ClinVar Genomic variation as it relates to human health
NM_001371596.2(MFSD8):c.1394G>A (p.Arg465Gln)
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.
Likely pathogenic(3); Uncertain significance(1)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_001371596.2(MFSD8):c.1394G>A (p.Arg465Gln)
Variation ID: 983438 Accession: VCV000983438.7
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 4q28.2 4: 127920793 (GRCh38) [ NCBI UCSC ] 4: 128841948 (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 Nov 6, 2020 Feb 4, 2024 Oct 24, 2022 - HGVS
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Nucleotide Protein Molecular
consequenceNM_001371596.2:c.1394G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001358525.1:p.Arg465Gln missense NM_001363520.3:c.1193G>A NP_001350449.1:p.Arg398Gln missense NM_001363521.3:c.1079G>A NP_001350450.1:p.Arg360Gln missense NM_001371590.2:c.1259G>A NP_001358519.1:p.Arg420Gln missense NM_001371591.2:c.1403G>A NP_001358520.1:p.Arg468Gln missense NM_001371592.2:c.1400G>A NP_001358521.1:p.Arg467Gln missense NM_001371593.2:c.1280G>A NP_001358522.1:p.Arg427Gln missense NM_001371594.2:c.1247G>A NP_001358523.1:p.Arg416Gln missense NM_001371595.1:c.1112G>A NP_001358524.1:p.Arg371Gln missense NM_001410765.1:c.944G>A NP_001397694.1:p.Arg315Gln missense NM_001410766.1:c.*966G>A NM_152778.3:c.1394G>A NM_152778.4:c.1394G>A NP_689991.1:p.Arg465Gln missense NC_000004.12:g.127920793C>T NC_000004.11:g.128841948C>T NG_008657.1:g.50192G>A LRG_833:g.50192G>A LRG_833t1:c.1394G>A LRG_833p1:p.Arg465Gln LRG_833t2:c.1394G>A LRG_833p2:p.Arg465Gln - Protein change
- R360Q, R371Q, R398Q, R416Q, R420Q, R427Q, R465Q, R467Q, R468Q, R315Q
- Other names
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- Canonical SPDI
- NC_000004.12:127920792:C:T
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
- Unknown function
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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
Help
The frequency of the allele represented by this VCV record.
The Genome Aggregation Database (gnomAD) 0.00001
Trans-Omics for Precision Medicine (TOPMed) 0.00001
- 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 | ||
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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
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. |
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MFSD8 | - | - |
GRCh38 GRCh37 |
946 | 992 |
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. |
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Likely pathogenic (2) |
criteria provided, multiple submitters, no conflicts
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Jan 11, 2022 | RCV002272437.4 | |
Conflicting interpretations of pathogenicity (2) |
criteria provided, conflicting classifications
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Oct 24, 2022 | RCV001263428.6 |
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. |
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Uncertain significance
(Oct 24, 2022)
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criteria provided, single submitter
Method: clinical testing
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Neuronal ceroid lipofuscinosis 7
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV003525608.1
First in ClinVar: Feb 07, 2023 Last updated: Feb 07, 2023 |
Comment:
This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 465 of the MFSD8 protein (p.Arg465Gln). … (more)
This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 465 of the MFSD8 protein (p.Arg465Gln). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with MFSD-related conditions (PMID: 21990111, 28586915, 33084218). ClinVar contains an entry for this variant (Variation ID: 983438). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. (less)
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Likely pathogenic
(Dec 10, 2021)
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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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Revvity Omics, Revvity
Accession: SCV003834010.2
First in ClinVar: Mar 04, 2023 Last updated: Feb 04, 2024 |
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Likely pathogenic
(-)
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criteria provided, single submitter
Method: clinical testing
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Neuronal ceroid lipofuscinosis 7
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
unknown
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Consultorio y Laboratorio de Neurogenética, Hospital JM Ramos Mejia
Accession: SCV001424316.1
First in ClinVar: Nov 06, 2020 Last updated: Nov 06, 2020 |
Sex: female
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Likely pathogenic
(Jan 11, 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: SCV002558418.2
First in ClinVar: Aug 08, 2022 Last updated: Mar 04, 2023 |
Comment:
Published functional studies demonstrate a damaging effect (Wang et al., 2021); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports … (more)
Published functional studies demonstrate a damaging effect (Wang et al., 2021); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Observed with a pathogenic variant in a patient with variant late-infantile neuronal ceroid lipofuscinosis, but it is not known whether the variants occurred on the same (in cis) or on different (in trans) chromosomes (Kousi et al., 2012); Observed with a possible hypomorphic variant on the opposite allele (in trans) in three siblings with late-onset isolated maculopathy (Khan et al.; 2017); This variant is associated with the following publications: (PMID: 34910516, 28586915, 31741823, 30487145, 21990111, 33084218) (less)
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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. |
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Unknown function
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Consultorio y Laboratorio de Neurogenética, Hospital JM Ramos Mejia
Accession: SCV001424316.1
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Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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The odyssey of complex neurogenetic disorders: From undetermined to positive. | Salinas V | American journal of medical genetics. Part C, Seminars in medical genetics | 2020 | PMID: 33084218 |
Specific Alleles of CLN7/MFSD8, a Protein That Localizes to Photoreceptor Synaptic Terminals, Cause a Spectrum of Nonsyndromic Retinal Dystrophy. | Khan KN | Investigative ophthalmology & visual science | 2017 | PMID: 28586915 |
Update of the mutation spectrum and clinical correlations of over 360 mutations in eight genes that underlie the neuronal ceroid lipofuscinoses. | Kousi M | Human mutation | 2012 | PMID: 21990111 |
Text-mined citations for rs1275962600 ...
HelpRecord last updated Jun 23, 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.