NM_003140.3(SRY):c.472C>T (p.Gln158Ter) AND 46,XY sex reversal 1

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Nov 28, 2023
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:: RCV003510490.2

Allele description [Variation Report for NM_003140.3(SRY):c.472C>T (p.Gln158Ter)]

NM_003140.3(SRY):c.472C>T (p.Gln158Ter)

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.472C>T (p.Gln158Ter)

HGVS:

NC_000024.10:g.2787132G>A
NG_011751.1:g.5620C>T
NM_003140.3:c.472C>TMANE SELECT
NP_003131.1:p.Gln158Ter
NC_000024.9:g.2655173G>A

Protein change:

Q158*

Molecular consequence:

NM_003140.3:c.472C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: 46,XY sex reversal 1
Synonyms:: 46,XY SEX REVERSAL, SRY-RELATED; SRY-related 46,XY complete gonadal dysgenesis
Identifiers:: MONDO: MONDO:0020712; MedGen: C2748896; Orphanet: 242; OMIM: 400044

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004252980	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Nov 28, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 7981695, 12919143, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004252980

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Nov 28, 2023)

germline

clinical testing

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

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

Citations

PubMed

A novel mutation localized in the 3' non-HMG box region of the SRY gene in 46,XY gonadal dysgenesis.

Tajima T, Nakae J, Shinohara N, Fujieda K.

Hum Mol Genet. 1994 Jul;3(7):1187-9. No abstract available.

PubMed [citation]

PMID:: 7981695

Two new point mutations of the SRY gene identified in two Italian 46,XY females with gonadal dysgenesis.

Baldazzi L, Nicoletti A, Gennari M, Barbaro M, Pirazzoli P, Cicognani A, Cacciari E.

Clin Genet. 2003 Sep;64(3):258-60. No abstract available. Erratum in: Clin Genet. 2003 Dec;64(6):526. Nicolettic A [corrected to Nicoletti A].

PubMed [citation]

PMID:: 12919143

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004252980.1

#	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 creates a premature translational stop signal (p.Gln158*) in the SRY gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 47 amino acid(s) of the SRY protein. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with SRY-related conditions. This variant disrupts the C-terminus of the SRY protein. Other variant(s) that disrupt this region (p.Gln158Hisfs*2, p.Leu163*) have been observed in individuals with SRY-related conditions (PMID: 7981695, 12919143). This suggests that this may be a clinically significant region of the protein. 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

Last Updated: Sep 29, 2024

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