VCV002664484.3 - ClinVar

NM_007241.4(SNF8):c.304G>A (p.Val102Ile)

Germline

Classification

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.

(3)

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.

Conflicting classifications of pathogenicity
Pathogenic(1); Uncertain significance(1)

criteria provided, conflicting classifications

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_007241.4(SNF8):c.304G>A (p.Val102Ile)

Variation ID: 2664484 Accession: VCV002664484.3

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 17q21.32 17: 48937065 (GRCh38) [ NCBI UCSC ] 17: 47014427 (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	Dec 9, 2023	May 1, 2024	Jan 30, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_007241.4:c.304G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_009172.2:p.Val102Ile	missense
NM_001317192.2:c.304G>A	NP_001304121.1:p.Val102Ile	missense
NM_001317193.2:c.253G>A	NP_001304122.1:p.Val85Ile	missense
NM_001317194.2:c.-88G>A		5 prime UTR
NM_007241.2:c.304G>A
NR_133679.2:n.412G>A		non-coding transcript variant
NC_000017.11:g.48937065C>T
NC_000017.10:g.47014427C>T

... more HGVS ... less HGVS

Protein change

V102I, V85I

Other names

Canonical SPDI

NC_000017.11:48937064:C:T

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele frequency (GMAF) Help The 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

OMIM: 610904.0005 VarSome

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
Gene	OMIM	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.
SNF8		-	-	GRCh38 GRCh37	17	33

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.
SNF8-associated disease	Pathogenic (1)	criteria provided, single submitter	Dec 7, 2023	RCV003447443.4
Neurodevelopmental disorder plus optic atrophy	Pathogenic (1)	no assertion criteria provided	Apr 10, 2024	RCV003994560.1
not specified	Uncertain significance (1)	criteria provided, single submitter	Jan 30, 2024	RCV004364705.1

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 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 (Dec 07, 2023)	criteria provided, single submitter (Classification criteria August 2017) Method: research	SNF8-associated disease Affected status: yes Allele origin: biparental	Institute of Human Genetics Munich, Klinikum Rechts Der Isar, TU München Accession: SCV004174814.1 First in ClinVar: Dec 09, 2023 Last updated: Dec 09, 2023
Uncertain significance (Jan 30, 2024)	criteria provided, single submitter (Ambry Variant Classification Scheme 2023) Method: clinical testing	not specified Affected status: unknown Allele origin: germline	Ambry Genetics Accession: SCV004952518.1 First in ClinVar: May 01, 2024 Last updated: May 01, 2024	Comment: The c.304G>A (p.V102I) alteration is located in exon 4 (coding exon 4) of the SNF8 gene. This alteration results from a G to A substitution … (more) The c.304G>A (p.V102I) alteration is located in exon 4 (coding exon 4) of the SNF8 gene. This alteration results from a G to A substitution at nucleotide position 304, causing the valine (V) at amino acid position 102 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. (less)
Pathogenic (Apr 10, 2024)	no assertion criteria provided Method: literature only	NEURODEVELOPMENTAL DISORDER PLUS OPTIC ATROPHY Affected status: not provided Allele origin: germline	OMIM Accession: SCV004812257.1 First in ClinVar: Apr 15, 2024 Last updated: Apr 15, 2024	Publications: PubMed (1) PubMed: 38423010 Comment on evidence: For discussion of the c.304G-A transition (c.304G-A, NM_007241.4) in the SNF8 gene, resulting in a val102-to-ile (V102I) substitution, that was identified in compound heterozygous state … (more) For discussion of the c.304G-A transition (c.304G-A, NM_007241.4) in the SNF8 gene, resulting in a val102-to-ile (V102I) substitution, that was identified in compound heterozygous state in a patient (patient F1) with neurodevelopmental disorder plus optic atrophy (NEDOA; 620784) by Brugger et al. (2024), see 610904.0003. In a patient (patient D1) with NEDOA, Brugger et al. (2024) identified compound heterozygosity for 2 mutations in the SNF8 gene, V102I and a c.423-1G-C transversion (610904.0006), predicted to result in a splicing abnormality. The mutations, which were identified by whole-exome sequencing and confirmed by Sanger sequencing, segregated with disease in the family. The c.423-1G-C mutation was not present in the gnomAD database (v4.0.0). In 2 sibs (patients E1 and E2) with NEDOA, Brugger et al. (2024) identified compound heterozygosity for 2 mutations in the SNF8 gene, V102I and a c.673_683delinsTGGA (610904.0007), predicted to result in an frameshift and premature termination (Asp225TrpfsTer99). The mutations, which were identified by whole-exome sequencing and confirmed by Sanger sequencing, were present in the carrier state in the parents. The c.673_683delinsTGGA mutation was not present in the gnomAD database (v4.0.0). (less)

Comment:

The c.304G>A (p.V102I) alteration is located in exon 4 (coding exon 4) of the SNF8 gene. This alteration results from a G to A substitution at nucleotide position 304, causing the valine (V) at amino acid position 102 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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.

Comment:

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Bi-allelic variants in SNF8 cause a disease spectrum ranging from severe developmental and epileptic encephalopathy to syndromic optic atrophy.	Brugger M	American journal of human genetics	2024	PMID: 38423010

Text-mined citations for this variant ...

Record last updated Jun 23, 2024

ClinVar Genomic variation as it relates to human health

NM_007241.4(SNF8):c.304G>A (p.Val102Ile)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...