chrY-2787278-A-G

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

Scores

10
2
3

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 3.84
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 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
SRYNM_003140.3 linkuse as main transcriptc.326T>C p.Phe109Ser missense_variant 1/1 ENST00000383070.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SRYENST00000383070.2 linkuse as main transcriptc.326T>C p.Phe109Ser missense_variant 1/1 NM_003140.3 P1
XGY2ENST00000681940.1 linkuse as main transcriptn.106+12539A>G intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes
Cov.:
0
GnomAD4 exome
Cov.:
1
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 providedliterature onlyOMIMDec 01, 1992- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.98
BayesDel_addAF
Pathogenic
0.63
D
BayesDel_noAF
Pathogenic
0.67
CADD
Benign
23
DANN
Uncertain
1.0
DEOGEN2
Pathogenic
0.90
D
FATHMM_MKL
Benign
0.62
D
LIST_S2
Benign
0.79
T
M_CAP
Pathogenic
1.0
D
MetaRNN
Pathogenic
0.99
D
MetaSVM
Pathogenic
1.1
D
MutationAssessor
Pathogenic
2.9
M
MutationTaster
Benign
1.0
A;A
PROVEAN
Pathogenic
-7.8
D
Sift
Uncertain
0.0080
D
Sift4G
Pathogenic
0.0
D
Polyphen
1.0
D
Vest4
0.94
MutPred
0.95
Gain of disorder (P = 0.0216);
MVP
0.99
MPC
1.5
ClinPred
0.98
D
GERP RS
0.64
Varity_R
0.92
gMVP
1.0

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs104894956; hg19: chrY-2655319; API