Homozugous variant in exon 7 of the APTX gene(chr9:g.32974554delA:depth 34x) that result in a frameshift and premature truncation of the protein 5 amino acid downstream codon 259 was detected. Baby Shaurya born of a non consanguineous marriage, presented with clinical indications of cerebellar ataxia, dyskinessia, imbalance while walking, extrapyramidal signs and abnormal limb movement. He is suspected to be affected with spinocerebellar disorders and has been evaluated for pathogenic gene variant. The p.Val259AspfsTer5 variant has not been reported in the 1000 Genomes and ExAC databases and has a minor allele frequency of 0.007% in our internal database. The in silico prediction of the variant is damaging by MutationTaster2. The reference region is conserved across mammals.
ClinVar Genomic variation as it relates to human health
NM_001195248.2(APTX):c.776del (p.Val259fs)
Germline
Classification
Help
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.
(2)
Help
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.
Pathogenic
2
criteria provided, multiple submitters, no conflicts
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_001195248.2(APTX):c.776del (p.Val259fs)
Variation ID: 635168 Accession: VCV000635168.2
- Type and length
-
Deletion, 1 bp
- Location
-
Cytogenetic: 9p21.1 9: 32974556 (GRCh38) [ NCBI UCSC ] 9: 32974554 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
-
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 Jun 28, 2019 Jan 21, 2023 Jun 20, 2019 - HGVS
-
... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_001195248.2:c.776del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001182177.2:p.Val259fs frameshift NM_001195249.2:c.776del NP_001182178.1:p.Val259fs frameshift NM_001195250.2:c.614del NP_001182179.2:p.Val205fs frameshift NM_001195251.2:c.776del NP_001182180.1:p.Val259fs frameshift NM_001195252.2:c.560del NP_001182181.2:p.Val187fs frameshift NM_001195254.2:c.614del NP_001182183.1:p.Val205fs frameshift NM_001368995.1:c.776del NP_001355924.1:p.Val259fs frameshift NM_001368996.1:c.776del NP_001355925.1:p.Val259fs frameshift NM_001368997.1:c.776del NP_001355926.1:p.Val259fs frameshift NM_001368998.1:c.776del NP_001355927.1:p.Val259fs frameshift NM_001368999.1:c.776del NP_001355928.1:p.Val259fs frameshift NM_001369000.1:c.614del NP_001355929.1:p.Val205fs frameshift NM_001369001.1:c.614del NP_001355930.1:p.Val205fs frameshift NM_001369002.1:c.512del NP_001355931.1:p.Val171fs frameshift NM_001369003.1:c.512del NP_001355932.1:p.Val171fs frameshift NM_001369004.1:c.512del NP_001355933.1:p.Val171fs frameshift NM_001369005.1:c.512del NP_001355934.1:p.Val171fs frameshift NM_001369006.1:c.512del NP_001355935.1:p.Val171fs frameshift NM_001370669.1:c.512del NP_001357598.1:p.Val171fs frameshift NM_001370670.1:c.512del NP_001357599.1:p.Val171fs frameshift NM_001370673.1:c.512del NP_001357602.1:p.Val171fs frameshift NM_175069.3:c.776del NP_778239.2:p.Val259fs frameshift NM_175073.2:c.776delT NM_175073.3:c.776del NP_778243.1:p.Val259fs frameshift NR_036577.2:n.727del non-coding transcript variant NR_160920.1:n.615del non-coding transcript variant NR_160921.1:n.746del non-coding transcript variant NR_160922.1:n.977del non-coding transcript variant NR_160923.1:n.781del non-coding transcript variant NR_160924.1:n.786del non-coding transcript variant NR_160925.1:n.982del non-coding transcript variant NR_160926.1:n.772del non-coding transcript variant NR_160927.1:n.865del non-coding transcript variant NR_160928.1:n.755del non-coding transcript variant NR_160929.1:n.669del non-coding transcript variant NR_160930.1:n.722del non-coding transcript variant NR_160931.1:n.961del non-coding transcript variant NC_000009.12:g.32974556del NC_000009.11:g.32974554del NG_012821.2:g.55576del - Protein change
- V187fs, V171fs, V259fs, V205fs
- Other names
- -
- Canonical SPDI
- NC_000009.12:32974555:A:
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
-
effect on regulatory function of DNA; Variation Ontology [ VariO:0152]
-
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.
- -
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
- -
- Links
Genes
| Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
|---|---|---|---|---|---|---|
| HI score
Help
The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
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. |
|||
| APTX | - | - |
GRCh38 GRCh37 |
289 | 358 | |
Conditions - Germline
| Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
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
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
|---|---|---|---|---|
| Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
|
Jun 20, 2019 | RCV000786024.3 |
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
Help
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
Help
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
Help
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. |
|
|---|---|---|---|---|---|
|
Pathogenic
(Jun 20, 2019)
|
criteria provided, single submitter
Method: clinical testing
|
Ataxia, early-onset, with oculomotor apraxia and hypoalbuminemia
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
inherited
|
Foundation for Research in Genetics and Endocrinology, FRIGE's Institute of Human Genetics
Accession: SCV000924631.1
First in ClinVar: Jun 28, 2019 Last updated: Jun 28, 2019 |
Comment:
Homozugous variant in exon 7 of the APTX gene(chr9:g.32974554delA:depth 34x) that result in a frameshift and premature truncation of the protein 5 amino acid downstream … (more)
Homozugous variant in exon 7 of the APTX gene(chr9:g.32974554delA:depth 34x) that result in a frameshift and premature truncation of the protein 5 amino acid downstream codon 259 was detected. Baby Shaurya born of a non consanguineous marriage, presented with clinical indications of cerebellar ataxia, dyskinessia, imbalance while walking, extrapyramidal signs and abnormal limb movement. He is suspected to be affected with spinocerebellar disorders and has been evaluated for pathogenic gene variant. The p.Val259AspfsTer5 variant has not been reported in the 1000 Genomes and ExAC databases and has a minor allele frequency of 0.007% in our internal database. The in silico prediction of the variant is damaging by MutationTaster2. The reference region is conserved across mammals. (less)
Clinical Features:
Dyskinesia (present) , Cerebellar ataxia (present) , Torticollis (present)
Age: 0-9 years
Sex: male
Ethnicity/Population group: Indian Hindu
Geographic origin: India
Method: DNA was used to perform targeted gene sequencing using a custom capture kit. Libraries were sequenced to mean >80-100X coverage in Illumina sequencing platform. Sequence obtained were aligned to a human reference genome using BWA program and analyzed using Picard and GATK-Lite toolkit to identify variants in the targeted genes relevant to clinical indication.
|
|
|
Pathogenic
(-)
|
criteria provided, single submitter
Method: clinical testing
|
Ataxia, early-onset, with oculomotor apraxia and hypoalbuminemia
Affected status: yes
Allele origin:
germline
|
Neuberg Centre For Genomic Medicine, NCGM
Accession: SCV002820178.1
First in ClinVar: Jan 21, 2023 Last updated: Jan 21, 2023 |
Comment:
This variant causes a frameshift starting with codon Valine 259, changes this amino acid to Aspartic Acid residue, and creates a premature Stop codon at … (more)
This variant causes a frameshift starting with codon Valine 259, changes this amino acid to Aspartic Acid residue, and creates a premature Stop codon at position 5 of the new reading frame, denoted p.Val259AspfsTer5. This variant has been reported as pathogenic to the ClinVar database. The p.Val259AspfsTer5 variant is novel (not in any individuals) in gnomAD Exomes and 1000 Genomes and has a minor allele frequency of 0.007%. The in silico prediction of the variant is damaging by MutationTaster2. The reference region is conserved across mammals. For these reasons, this variant has been classified as Pathogenic (less)
Clinical Features:
Global developmental delay (present) , Cerebellar ataxia (present)
|
Comment:
Comment:
This variant causes a frameshift starting with codon Valine 259, changes this amino acid to Aspartic Acid residue, and creates a premature Stop codon at position 5 of the new reading frame, denoted p.Val259AspfsTer5. This variant has been reported as pathogenic to the ClinVar database. The p.Val259AspfsTer5 variant is novel (not in any individuals) in gnomAD Exomes and 1000 Genomes and has a minor allele frequency of 0.007%. The in silico prediction of the variant is damaging by MutationTaster2. The reference region is conserved across mammals. For these reasons, this variant has been classified as Pathogenic
Germline Functional Evidence
| Functional
Help
The functional consequence of the variant, based on experimental evidence and provided by the submitter. consequence |
Method
Help
A brief description of the method used to determine the functional consequence of the variant. A citation for the method is included, when provided by the submitter. |
Result
Help
A brief description of the result of this method for this variant. |
Submitter
Help
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
Help
This column includes more information supporting functional evidence for the germline classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
|---|---|---|---|---|
|
effect on regulatory function of DNA
|
Foundation for Research in Genetics and Endocrinology, FRIGE's Institute of Human Genetics
Accession: SCV000924631.1
|
|
Comment:
Homozugous variant in exon 7 of the APTX gene(chr9:g.32974554delA:depth 34x) that result in a frameshift and premature truncation of the protein 5 amino acid downstream codon 259 was detected. Baby Shaurya born of a non consanguineous marriage, presented with clinical indications of cerebellar ataxia, dyskinessia, imbalance while walking, extrapyramidal signs and abnormal limb movement. He is suspected to be affected with spinocerebellar disorders and has been evaluated for pathogenic gene variant. The p.Val259AspfsTer5 variant has not been reported in the 1000 Genomes and ExAC databases and has a minor allele frequency of 0.007% in our internal database. The in silico prediction of the variant is damaging by MutationTaster2. The reference region is conserved across mammals.
Comment:
This variant causes a frameshift starting with codon Valine 259, changes this amino acid to Aspartic Acid residue, and creates a premature Stop codon at position 5 of the new reading frame, denoted p.Val259AspfsTer5. This variant has been reported as pathogenic to the ClinVar database. The p.Val259AspfsTer5 variant is novel (not in any individuals) in gnomAD Exomes and 1000 Genomes and has a minor allele frequency of 0.007%. The in silico prediction of the variant is damaging by MutationTaster2. The reference region is conserved across mammals. For these reasons, this variant has been classified as Pathogenic
Citations for germline classification of this variant
Help| There are no citations for germline classification of this variant in ClinVar. If you know of citations for this variation, please consider submitting that information to ClinVar. |
Text-mined citations for rs1563945076 ...
HelpThese citations are identified by LitVar using
the rs number, so they may include citations for more than one variant
at this location. Please review the LitVar results carefully for your
variant of interest.
Record last updated Apr 06, 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.