NM_003140.3(SRY):c.178G>C (p.Val60Leu) AND not provided

Germline classification:: Pathogenic (1 submission)
Last evaluated:: May 24, 2022
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:: RCV002460889.1

Allele description [Variation Report for NM_003140.3(SRY):c.178G>C (p.Val60Leu)]

NM_003140.3(SRY):c.178G>C (p.Val60Leu)

Gene:

SRY:sex determining region Y [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

Yp11.2

Genomic location:

Preferred name:

NM_003140.3(SRY):c.178G>C (p.Val60Leu)

HGVS:

NC_000024.10:g.2787426C>G
NG_011751.1:g.5326G>C
NM_003140.3:c.178G>CMANE SELECT
NP_003131.1:p.Val60Leu
NC_000024.9:g.2655467C>G
NM_003140.1:c.178G>C
Q05066:p.Val60Leu

Protein change:

V60L; VAL60LEU

Links:

UniProtKB: Q05066#VAR_003719; OMIM: 480000.0004; dbSNP: rs104894957

NCBI 1000 Genomes Browser:

rs104894957

Molecular consequence:

NM_003140.3:c.178G>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: CN517202

Recent activity

Clear Turn Off Turn On

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
SCV002757498	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (May 24, 2022)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002757498

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Pathogenic
(May 24, 2022)

germline

clinical testing

Citation Link

Help

Summary from all submissions

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

Details of each submission

From GeneDx, SCV002757498.1

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

Description

Reported in one family with several affected females with 46,XY gonadal dysgenesis, including sisters who inherited the variant from their unaffected father (Berta et al., 1990; Vilain et al., 1992); Published functional studies demonstrate V60L damages transcriptional activation and repression of target genes, subcellular localization, phosphorylation, protein stability, and Wnt/B-catenin signaling (Phillips et al., 2011; Chen et al., 2013); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Missense variants in this gene are often considered pathogenic (HGMD); Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 18675318, 21849498, 1734522, 24003159, 1570829, 10690846, 2247149)

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

Last Updated: Feb 7, 2023

ClinVar

Relating variation to medicine