NM_003140.2(SRY):c.326T>C (p.Phe109Ser) AND 46,XY sex reversal, type 1

Clinical significance:Pathogenic (Last evaluated: Dec 1, 1992)

Review status:(0/4) 0 stars out of maximum of 4 stars

no assertion criteria provided

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000010391.4

Allele description [Variation Report for NM_003140.2(SRY):c.326T>C (p.Phe109Ser)]

NM_003140.2(SRY):c.326T>C (p.Phe109Ser)

Gene:
SRY:sex determining region Y [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Yp11.2
Genomic location:
Preferred name:
NM_003140.2(SRY):c.326T>C (p.Phe109Ser)
HGVS:
  • NC_000024.10:g.2787278A>G
  • NG_011751.1:g.5474T>C
  • NM_003140.2:c.326T>C
  • NP_003131.1:p.Phe109Ser
  • NC_000024.9:g.2655319A>G
  • NM_003140.1:c.326T>C
  • Q05066:p.Phe109Ser
Protein change:
F109S; PHE109SER
Links:
UniProtKB: Q05066#VAR_003730; OMIM: 480000.0003; dbSNP: 104894956
NCBI 1000 Genomes Browser:
rs104894956
Molecular consequence:
  • NM_003140.2:c.326T>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
46,XY sex reversal, type 1 (SRXY1)
Synonyms:
46,XY SEX REVERSAL, SRY-RELATED; SRY-related 46,XY complete gonadal dysgenesis
Identifiers:
MedGen: C2748896; Orphanet: 242; OMIM: 400044
Age of onset:
Adolescent

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000030617OMIMno assertion criteria providedPathogenic
(Dec 1, 1992)
germlineliterature only

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only

Citations

PubMed

A familial mutation in the testis-determining gene SRY shared by both sexes.

J├Ąger RJ, Harley VR, Pfeiffer RA, Goodfellow PN, Scherer G.

Hum Genet. 1992 Dec;90(4):350-5.

PubMed [citation]
PMID:
1483689

Details of each submission

From OMIM, SCV000030617.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (1)

Description

In an XY female with gonadal dysgenesis (SRXY1; 400044), her father, her 2 brothers and an uncle, Jager et al. (1992) found a T-to-C transition in the region of the SRY gene coding for a protein motif known as the high mobility group (HMG) box, a protein domain known to confer DNA-binding specificity on the SRY protein. The mutation resulted in the substitution, at amino acid position 109, of a serine residue for phenylalanine, a conserved aromatic residue in almost all HMG box motifs known. This F109S mutation was not found in 176 male controls. When recombinant wildtype SRY and SRY(F109S) mutant protein were tested in vitro for binding to the target site AAC AAAG, no differences in DNA-binding activity were observed. These results implied that the F109S mutation either is a rare neutral sequence variant, or produces an SRY protein with slightly altered in vivo activity, the resulting sex phenotype depending on the genetic background or environmental factors. The proband had primary amenorrhea and was 180 cm tall. Prior to therapy, mammary development was at stage III (Tanner). No signs of virilization were found. At laparotomy, bilateral streak gonads, atrophic fallopian tubes, and a rudimentary uterus with a narrow lumen were detected. Although the paternal uncle with the F109S mutation had an undescended right testis, the family was unremarkable with regard to infertility, gynecologic tumors, and abnormal sex phenotypes.

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

Last Updated: Apr 7, 2017