ClinVar Genomic variation as it relates to human health
NM_001008537.3(NEXMIF):c.3458dup (p.Asn1153fs)
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_001008537.3(NEXMIF):c.3458dup (p.Asn1153fs)
Variation ID: 653605 Accession: VCV000653605.10
- Type and length
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Duplication, 1 bp
- Location
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Cytogenetic: Xq13.3 X: 74741098-74741099 (GRCh38) [ NCBI UCSC ] X: 73960933-73960934 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Aug 14, 2019 May 1, 2024 Oct 10, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_001008537.3:c.3458dup MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001008537.1:p.Asn1153fs frameshift NM_001008537.1:c.3458dup NM_001008537.2:c.3458dupA NC_000023.11:g.74741105dup NC_000023.10:g.73960940dup NG_027726.1:g.189354dup - Protein change
- N1153fs
- Other names
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- Canonical SPDI
- NC_000023.11:74741098:TTTTTTT:TTTTTTTT
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
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Allele frequency
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The frequency of the allele represented by this VCV record.
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- Links
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
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Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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HI score
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The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
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The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
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The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
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The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
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NEXMIF | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
990 | 1126 |
Conditions - Germline
Condition
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The condition for this variant-condition (RCV) record in ClinVar. |
Classification
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The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
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The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
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The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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Pathogenic (3) |
criteria provided, multiple submitters, no conflicts
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Jan 3, 2022 | RCV001809825.4 | |
Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
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Oct 10, 2023 | RCV000809404.5 | |
Pathogenic (1) |
criteria provided, single submitter
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Aug 2, 2021 | RCV004028664.1 |
Submissions - Germline
Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
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The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
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The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
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This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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Pathogenic
(Oct 10, 2023)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV000949554.4
First in ClinVar: Aug 14, 2019 Last updated: Feb 14, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Asn1153Lysfs*8) in the NEXMIF gene. It is expected to result in an absent or disrupted protein … (more)
This sequence change creates a premature translational stop signal (p.Asn1153Lysfs*8) in the NEXMIF gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in NEXMIF are known to be pathogenic (PMID: 23615299). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with NEXMIF encephalopathy (PMID: 33144681). ClinVar contains an entry for this variant (Variation ID: 653605). For these reasons, this variant has been classified as Pathogenic. (less)
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Pathogenic
(Jan 03, 2022)
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criteria provided, single submitter
Method: clinical testing
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X-linked intellectual disability, Cantagrel type
Affected status: yes
Allele origin:
germline
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3billion
Accession: SCV002059025.1
First in ClinVar: Jan 15, 2022 Last updated: Jan 15, 2022 |
Comment:
Frameshift: predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported … (more)
Frameshift: predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported downstream of the variant (PVS1_VS). It is not observed in the gnomAD v2.1.1 dataset (PM2_M). The variant has been reported to be associated with NEXMIF related disorder (ClinVar ID: VCV000653605). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline. (less)
Clinical Features:
Epileptic encephalopathy (present) , Intellectual disability (present) , Myoclonus (present) , Aggressive behavior (present)
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Pathogenic
(Jul 14, 2022)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV002820735.1
First in ClinVar: Jan 21, 2023 Last updated: Jan 21, 2023 |
Comment:
Frameshift variant predicted to result in protein truncation or nonsense-mediated decay in a gene for which loss of function is a known mechanism of disease; … (more)
Frameshift variant predicted to result in protein truncation or nonsense-mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 33767182, 33144681) (less)
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Pathogenic
(-)
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criteria provided, single submitter
Method: clinical testing
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X-linked intellectual disability, Cantagrel type
(X-linked dominant inheritance)
Affected status: yes
Allele origin:
germline
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Neuberg Centre For Genomic Medicine, NCGM
Accession: SCV004100629.1
First in ClinVar: Nov 04, 2023 Last updated: Nov 04, 2023 |
Comment:
The frameshift duplication p.N1153Kfs*8 in NEXMIF (NM_001008537.3) has been reported previously in affected individuals (Stamberger H et al,2021). It has been submitted previously to ClinVar … (more)
The frameshift duplication p.N1153Kfs*8 in NEXMIF (NM_001008537.3) has been reported previously in affected individuals (Stamberger H et al,2021). It has been submitted previously to ClinVar as Pathogenic. The p.N1153Kfs*8 variant is novel (not in any individuals) in gnomAD Exomes and is novel (not in any individuals) in 1000 Genomes. This variant is predicted to cause loss of normal protein function. Loss of function variants have been previously reported to be disease causing. For these reasons, this variant has been classified as Pathogenic. (less)
Clinical Features:
Intellectual disability (present)
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Pathogenic
(Aug 29, 2018)
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criteria provided, single submitter
Method: clinical testing
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X-linked intellectual disability, Cantagrel type
Affected status: unknown
Allele origin:
unknown
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Illumina Laboratory Services, Illumina
Accession: SCV004801623.1
First in ClinVar: Mar 23, 2024 Last updated: Mar 23, 2024 |
Comment:
The KIAA2022 c.3458dupA p.(Asn1153LysfsTer8) variant causes a shift in the protein reading frame that is predicted to result in premature termination of the protein. Loss … (more)
The KIAA2022 c.3458dupA p.(Asn1153LysfsTer8) variant causes a shift in the protein reading frame that is predicted to result in premature termination of the protein. Loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay is expected. To our knowledge, this variant has not been reported in the peer-reviewed literature. This variant is not observed in version 2.1.1 of the Genome Aggregation Database. The variant was identified in a de novo state in the proband. Based on the available evidence the c.3458dupA p.(Asn1153LysfsTer8) variant is classified as pathogenic for X-linked intellectual developmental disorder. (less)
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Pathogenic
(Aug 02, 2021)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: unknown
Allele origin:
germline
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Ambry Genetics
Accession: SCV003676360.2
First in ClinVar: Feb 07, 2023 Last updated: May 01, 2024 |
Comment:
The c.3458dupA (p.N1153Kfs*8) alteration, located in exon 3 (coding exon 2) of the KIAA2022 gene, consists of a duplication of A at position 3458, causing … (more)
The c.3458dupA (p.N1153Kfs*8) alteration, located in exon 3 (coding exon 2) of the KIAA2022 gene, consists of a duplication of A at position 3458, causing a translational frameshift with a predicted alternate stop codon after 8 amino acids. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. Based on the available evidence, this alteration is classified as pathogenic. (less)
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Germline Functional Evidence
There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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NEXMIF encephalopathy: an X-linked disorder with male and female phenotypic patterns. | Stamberger H | Genetics in medicine : official journal of the American College of Medical Genetics | 2021 | PMID: 33144681 |
Loss of function of KIAA2022 causes mild to severe intellectual disability with an autism spectrum disorder and impairs neurite outgrowth. | Van Maldergem L | Human molecular genetics | 2013 | PMID: 23615299 |
Text-mined citations for rs1602211123 ...
HelpRecord last updated May 19, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.