NM_004656.4(BAP1):c.1721C>T (p.Ala574Val) AND BAP1-related tumor predisposition syndrome

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Mar 13, 2024
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000464695.10

Allele description [Variation Report for NM_004656.4(BAP1):c.1721C>T (p.Ala574Val)]

NM_004656.4(BAP1):c.1721C>T (p.Ala574Val)

Gene:

BAP1:BRCA1 associated deubiquitinase 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

3p21.1

Genomic location:

Preferred name:

NM_004656.4(BAP1):c.1721C>T (p.Ala574Val)

HGVS:

NC_000003.12:g.52403424G>A
NG_031859.1:g.11570C>T
NM_004656.4:c.1721C>TMANE SELECT
NP_004647.1:p.Ala574Val
LRG_529t1:c.1721C>T
LRG_529:g.11570C>T
NC_000003.11:g.52437440G>A
NM_004656.2:c.1721C>T
NM_004656.3:c.1721C>T

Protein change:

A574V

Links:

dbSNP: rs761596789

NCBI 1000 Genomes Browser:

rs761596789

Molecular consequence:

NM_004656.4:c.1721C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: BAP1-related tumor predisposition syndrome (TPDS1)
Synonyms:: Tumor predisposition syndrome; Tumor susceptibility linked to germline BAP1 mutations; BAP1 tumor predisposition syndrome; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0013692; MedGen: C3280492; Orphanet: 289539; OMIM: 614327

Recent activity

Clear Turn Off Turn On

XPNPEP2 [Anser cygnoides]
XPNPEP2 [Anser cygnoides]
Gene ID:106037639

Gene
ENSPANP00000015399 (0)
Protein
groundwater metagenome
groundwater metagenome
groundwater metagenome Genome sequencing and assembly

BioProject
BioProject Links for Protein (Select 1308826163) (1)
BioProject
Taxonomy Links for Protein (Select 1308826155) (1)
Taxonomy

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000553948	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jan 16, 2024)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 25974357, 28062663, 28492532
SCV005053258	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Mar 13, 2024)	unknown	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

SCV000553948

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jan 16, 2024)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

SCV005053258

Baylor Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Mar 13, 2024)

unknown

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	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Clinical Characteristics of Uveal Melanoma in Patients With Germline BAP1 Mutations.

Gupta MP, Lane AM, DeAngelis MM, Mayne K, Crabtree M, Gragoudas ES, Kim IK.

JAMA Ophthalmol. 2015 Aug;133(8):881-7. doi: 10.1001/jamaophthalmol.2015.1119.

PubMed [citation]

PMID:: 25974357

A population-based analysis of germline BAP1 mutations in melanoma.

O'Shea SJ, Robles-Espinoza CD, McLellan L, Harrigan J, Jacq X, Hewinson J, Iyer V, Merchant W, Elliott F, Harland M, Bishop DT, Newton-Bishop JA, Adams DJ.

Hum Mol Genet. 2017 Feb 15;26(4):717-728. doi: 10.1093/hmg/ddw403.

PubMed [citation]

PMID:: 28062663
PMCID:: PMC5409081

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000553948.8

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 574 of the BAP1 protein (p.Ala574Val). This variant is present in population databases (rs761596789, gnomAD 0.003%). This missense change has been observed in individual(s) with uveal melanoma (PMID: 25974357). ClinVar contains an entry for this variant (Variation ID: 412422). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt BAP1 protein function with a negative predictive value of 80%. Experimental studies have shown that this missense change does not substantially affect BAP1 function (PMID: 28062663). 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.

#	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		not provided	not provided	not provided	not provided

From Baylor Genetics, SCV005053258.1

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

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

Last Updated: Sep 29, 2024

ClinVar

Relating variation to medicine