Y-2787341-G-C

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PVS1_StrongPP5_Moderate

The NM_003140.3(SRY):​c.263C>G​(p.Ser88*) variant causes a stop gained change. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★).

Frequency

Genomes: not found (cov: 0)

Consequence

SRY
NM_003140.3 stop_gained

Scores

2
3

Clinical Significance

Likely pathogenic criteria provided, single submitter P:1

Conservation

PhyloP100: 7.09
Variant links:
Genes affected
SRY (HGNC:11311): (sex determining region Y) This intronless gene encodes a transcription factor that is a member of the high mobility group (HMG)-box family of DNA-binding proteins. This protein is the testis-determining factor (TDF), which initiates male sex determination. Mutations in this gene give rise to XY females with gonadal dysgenesis (Swyer syndrome); translocation of part of the Y chromosome containing this gene to the X chromosome causes XX male syndrome. [provided by RefSeq, Jul 2008]
XGY2 (HGNC:34022): (XG Y-linked 2 (pseudogene))

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. There are 5 pathogenic variants in the truncated region.
PP5
Variant Y-2787341-G-C is Pathogenic according to our data. Variant chrY-2787341-G-C is described in ClinVar as [Likely_pathogenic]. Clinvar id is 2431744.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SRYNM_003140.3 linkc.263C>G p.Ser88* stop_gained Exon 1 of 1 ENST00000383070.2 NP_003131.1 Q05066A7WPU8

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SRYENST00000383070.2 linkc.263C>G p.Ser88* stop_gained Exon 1 of 1 6 NM_003140.3 ENSP00000372547.1 Q05066

Frequencies

GnomAD3 genomes
Cov.:
0
GnomAD4 exome
Cov.:
3
GnomAD4 genome
Cov.:
0

ClinVar

Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

46,XY sex reversal 1 Pathogenic:1
Aug 31, 2022
Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein
Significance: Likely pathogenic
Review Status: criteria provided, single submitter
Collection Method: clinical testing

ACMG classification criteria: PVS1 strong, PM2 moderated -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
0.70
D
BayesDel_noAF
Pathogenic
0.50
CADD
Pathogenic
33
DANN
Benign
0.96
FATHMM_MKL
Benign
0.75
D
Vest4
0.74
GERP RS
0.64

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chrY-2655382; API