chrY-2787278-A-G
Position:
Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM1PP3_StrongPP5
The NM_003140.3(SRY):c.326T>C(p.Phe109Ser) variant causes a missense change. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: not found (cov: 0)
Consequence
SRY
NM_003140.3 missense
NM_003140.3 missense
Scores
10
2
3
Clinical Significance
Conservation
PhyloP100: 3.84
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 7 ACMG points.
PM1
In a hotspot region, there are 3 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 0 benign, 2 uncertain in NM_003140.3
PP3
MetaRNN computational evidence supports a deleterious effect, 0.995
PP5
Variant Y-2787278-A-G is Pathogenic according to our data. Variant chrY-2787278-A-G is described in ClinVar as [Pathogenic]. Clinvar id is 9738.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SRY | NM_003140.3 | c.326T>C | p.Phe109Ser | missense_variant | 1/1 | ENST00000383070.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SRY | ENST00000383070.2 | c.326T>C | p.Phe109Ser | missense_variant | 1/1 | NM_003140.3 | P1 | ||
XGY2 | ENST00000681940.1 | n.106+12539A>G | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes Cov.: 0
GnomAD3 genomes
Cov.:
0
GnomAD4 exome Cov.: 1
GnomAD4 exome
Cov.:
1
GnomAD4 genome Cov.: 0
GnomAD4 genome
Cov.:
0
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
46,XY sex reversal 1 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Dec 01, 1992 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Benign
DANN
Uncertain
DEOGEN2
Pathogenic
D
FATHMM_MKL
Benign
D
LIST_S2
Benign
T
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D
MetaSVM
Pathogenic
D
MutationAssessor
Pathogenic
M
MutationTaster
Benign
A;A
PROVEAN
Pathogenic
D
Sift
Uncertain
D
Sift4G
Pathogenic
D
Polyphen
D
Vest4
MutPred
Gain of disorder (P = 0.0216);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at