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NM_003140.3(SRY):c.264dup (p.Glu89fs) AND 46,XY sex reversal 1

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Jun 3, 2017
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:
RCV000528652.7

Allele description [Variation Report for NM_003140.3(SRY):c.264dup (p.Glu89fs)]

NM_003140.3(SRY):c.264dup (p.Glu89fs)

Gene:
SRY:sex determining region Y [Gene - OMIM - HGNC]
Variant type:
Duplication
Cytogenetic location:
Yp11.2
Genomic location:
Preferred name:
NM_003140.3(SRY):c.264dup (p.Glu89fs)
HGVS:
  • NC_000024.10:g.2787340dup
  • NG_011751.1:g.5412dup
  • NM_003140.3:c.264dupMANE SELECT
  • NP_003131.1:p.Glu89fs
  • NC_000024.9:g.2655380_2655381insT
  • NC_000024.9:g.2655381dup
  • NM_003140.2:c.264dupA
Protein change:
E89fs
Links:
dbSNP: rs1556370556
NCBI 1000 Genomes Browser:
rs1556370556
Molecular consequence:
  • NM_003140.3:c.264dup - frameshift variant - [Sequence Ontology: SO:0001589]

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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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000647882Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Jun 3, 2017) 		germlineclinical testing

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

A human XY female with a frame shift mutation in the candidate testis-determining gene SRY.

Jäger RJ, Anvret M, Hall K, Scherer G.

Nature. 1990 Nov 29;348(6300):452-4.

PubMed [citation]
PMID:
2247151

Identification of a novel mutation in the SRY gene in a 46, XY female patient.

Salehi LB, Scarciolla O, Vanni GF, Nardone AM, Frajese G, Novelli G, Stuppia L.

Eur J Med Genet. 2006 Nov-Dec;49(6):494-8. Epub 2006 Apr 17.

PubMed [citation]
PMID:
16675314
See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000647882.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

This variant is not present in population databases (ExAC no frequency). For these reasons, this variant has been classified as Pathogenic. A different truncation downstream of this variant (p.Glu122Asnfs*58) has been determined to be pathogenic (PMID: 2247151). This suggests that deletion of this region of the SRY protein is causative of disease. This variant has been reported in an individual affected with complete 46, XY gonadal dysgenesis (PMID: 16675314). This sequence change results in a premature translational stop signal in the SRY gene (p.Glu89Argfs*15). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 116 amino acids of the SRY protein.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2024