NM_001354604.2(MITF):c.1412A>T (p.Tyr471Phe) AND not specified

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Feb 25, 2021
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000825959.5

Allele description [Variation Report for NM_001354604.2(MITF):c.1412A>T (p.Tyr471Phe)]

NM_001354604.2(MITF):c.1412A>T (p.Tyr471Phe)

Gene:

MITF:melanocyte inducing transcription factor [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

3p13

Genomic location:

Preferred name:

NM_001354604.2(MITF):c.1412A>T (p.Tyr471Phe)

HGVS:

NC_000003.12:g.69965079A>T
NG_011631.1:g.230598A>T
NM_000248.4:c.1091A>T
NM_001184967.2:c.1238A>T
NM_001354604.2:c.1412A>TMANE SELECT
NM_001354605.2:c.1409A>T
NM_001354606.2:c.1391A>T
NM_001354607.2:c.1343A>T
NM_001354608.2:c.1238A>T
NM_006722.3:c.1391A>T
NM_198158.3:c.1073A>T
NM_198159.3:c.1394A>T
NM_198177.3:c.1346A>T
NM_198178.3:c.905A>T
NP_000239.1:p.Tyr364Phe
NP_000239.1:p.Tyr364Phe
NP_001171896.1:p.Tyr413Phe
NP_001341533.1:p.Tyr471Phe
NP_001341534.1:p.Tyr470Phe
NP_001341535.1:p.Tyr464Phe
NP_001341536.1:p.Tyr448Phe
NP_001341537.1:p.Tyr413Phe
NP_006713.1:p.Tyr464Phe
NP_937801.1:p.Tyr358Phe
NP_937802.1:p.Tyr465Phe
NP_937820.1:p.Tyr449Phe
NP_937821.2:p.Tyr302Phe
LRG_776t1:c.1091A>T
LRG_776:g.230598A>T
LRG_776p1:p.Tyr364Phe
NC_000003.11:g.70014230A>T
NM_000248.3:c.1091A>T
NM_198159.2:c.1394A>T
p.Tyr465Phe

Protein change:

Y302F

Links:

dbSNP: rs145325518

NCBI 1000 Genomes Browser:

rs145325518

Molecular consequence:

NM_000248.4:c.1091A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001184967.2:c.1238A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001354604.2:c.1412A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001354605.2:c.1409A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001354606.2:c.1391A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001354607.2:c.1343A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001354608.2:c.1238A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_006722.3:c.1391A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_198158.3:c.1073A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_198159.3:c.1394A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_198177.3:c.1346A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_198178.3:c.905A>T - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000967444	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	criteria provided, single submitter (LMM Criteria)	Uncertain significance (Feb 25, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000967444

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

criteria provided, single submitter

(LMM Criteria)

Uncertain significance
(Feb 25, 2021)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	2	1	not provided	not provided	not provided	clinical testing

Citations

PubMed

A systematic approach to assessing the clinical significance of genetic variants.

Duzkale H, Shen J, McLaughlin H, Alfares A, Kelly MA, Pugh TJ, Funke BH, Rehm HL, Lebo MS.

Clin Genet. 2013 Nov;84(5):453-63. doi: 10.1111/cge.12257.

PubMed [citation]

PMID:: 24033266
PMCID:: PMC3995020

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV000967444.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	2	not provided	not provided	clinical testing	PubMed (1)

Description

Variant classified as Uncertain Significance - Favor Benign. The p.Tyr465Phe variant in MITF has not been previously reported in individuals with hearing loss or Waardenburg syndrome, but has been identified in 0.088% (22/24974) of African chromosomes by gnomAD (http://gnomad.broadinstitute.org; dbSNP rs14532518). Although this variant has been seen in the general population, its frequency is not high enough to rule out a pathogenic role. Computational prediction tools and conservation analysis suggest that the p.Tyr465Phe variant may not impact the protein, though this information is not predictive enough to rule out pathogenicity. Three species (tetraodon, fugu, yellowbelly pufferfish) carry a Phe at this position despite high nearby amino acid conservation. In summary, while the clinical significance of this variant is uncertain, these data suggest that it is more likely to be benign. ACMG/AMP Criteria applied: BP4

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		2	not provided	1	not provided

Last Updated: Sep 29, 2024

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