VCV002938197.4 - ClinVar

NM_001354604.2(MITF):c.828C>A (p.Thr276=)

Germline

Classification

criteria provided, multiple submitters, no conflicts. Learn more about how ClinVar calculates review status.

Likely benign

2 out of 2 submissions contributed to this 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.

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_001354604.2(MITF):c.828C>A (p.Thr276=)

Variation ID: 2938197 Accession: VCV002938197.4

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 3p13 3: 69949116 (GRCh38) [ NCBI UCSC ] 3: 69998267 (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	Feb 29, 2024	Feb 23, 2026	May 17, 2025

HGVS

Nucleotide	Protein	Molecular consequence
NM_001354604.2:c.828C>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_001341533.1:p.Thr276=	synonymous
NM_000248.4:c.507C>A MANE Plus Clinical Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_000239.1:p.Thr169=	synonymous
NM_001184967.2:c.672C>A	NP_001171896.1:p.Thr224=	synonymous
NM_001354605.2:c.825C>A	NP_001341534.1:p.Thr275=	synonymous
NM_001354606.2:c.825C>A	NP_001341535.1:p.Thr275=	synonymous
NM_001354607.2:c.777C>A	NP_001341536.1:p.Thr259=	synonymous
NM_001354608.2:c.672C>A	NP_001341537.1:p.Thr224=	synonymous
NM_006722.3:c.825C>A	NP_006713.1:p.Thr275=	synonymous
NM_198158.3:c.507C>A	NP_937801.1:p.Thr169=	synonymous
NM_198159.3:c.828C>A	NP_937802.1:p.Thr276=	synonymous
NM_198177.3:c.780C>A	NP_937820.1:p.Thr260=	synonymous
NM_198178.3:c.339C>A	NP_937821.2:p.Thr113=	synonymous
NC_000003.12:g.69949116C>A
NC_000003.11:g.69998267C>A
NG_011631.1:g.214635C>A
LRG_776:g.214635C>A
LRG_776t1:c.507C>A	LRG_776p1:p.Thr169=

... more HGVS ... less HGVS

Protein change

Other names

Canonical SPDI

NC_000003.12:69949115:C:A

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.

Trans-Omics for Precision Medicine (TOPMed) 0.00000

The Genome Aggregation Database (gnomAD) 0.00001

Exome Aggregation Consortium (ExAC) 0.00002

Links

ClinGen: CA2490483 dbSNP: rs750962324 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.
MITF		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	1302	1333

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.
Melanoma, cutaneous malignant, susceptibility to, 8 Tietz syndrome Waardenburg syndrome type 2A	Likely benign (1)	criteria provided, single submitter	Aug 3, 2023	RCV003797019.4
Hereditary cancer-predisposing syndrome	Likely benign (1)	criteria provided, single submitter	May 17, 2025	RCV005602089.1

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.	Expand all rows Collapse all rows 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.
Likely benign (May 17, 2025) C Contributing to aggregate classification	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Hereditary cancer-predisposing syndrome	Ambry Genetics Accession: SCV006272125.1 First in ClinVar: Jul 13, 2025 Last updated: Jul 13, 2025	Comment: show This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Likely benign (Aug 03, 2023) C Contributing to aggregate classification	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Melanoma, cutaneous malignant, susceptibility to, 8 Waardenburg syndrome type 2A Tietz syndrome Explanation for multiple conditions: Uncertain. The variant was classified for several related diseases, possibly a spectrum of disease; the variant may be associated with one or more the diseases.	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV004586031.3 First in ClinVar: Feb 28, 2024 Last updated: Feb 23, 2026	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Comment:

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.

Citations for germline classification of this variant

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 rs750962324 ...

These 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 Feb 25, 2026