rs104894969
Positions:
Variant summary
Our verdict is Likely pathogenic. Variant got 9 ACMG points: 9P and 0B. PM1PM5PP3_StrongPP5
The NM_003140.3(SRY):c.192G>A(p.Met64Ile) 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). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M64R) has been classified as Likely pathogenic.
Frequency
Genomes: not found (cov: 0)
Consequence
SRY
NM_003140.3 missense
NM_003140.3 missense
Scores
9
4
2
Clinical Significance
Conservation
PhyloP100: 5.68
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 9 ACMG points.
PM1
?
In a DNA_binding_region HMG box (size 68) in uniprot entity SRY_HUMAN there are 28 pathogenic changes around while only 0 benign (100%) in NM_003140.3
PM5
?
Other missense variant is known to change same aminoacid residue: Variant chrnull-null-null-null is described in UniProt as null.
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.992
PP5
?
Variant Y-2787412-C-T is Pathogenic according to our data. Variant chrY-2787412-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 9747.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.192G>A | p.Met64Ile | missense_variant | 1/1 | ENST00000383070.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SRY | ENST00000383070.2 | c.192G>A | p.Met64Ile | missense_variant | 1/1 | NM_003140.3 | P1 | ||
XGY2 | ENST00000681940.1 | n.106+12673C>T | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? Cov.: 0
GnomAD3 genomes
?
Cov.:
0
GnomAD4 exome Cov.: 16
GnomAD4 exome
Cov.:
16
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 | Nov 29, 1990 | - - |
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
Uncertain
D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D
MetaSVM
Pathogenic
D
MutationAssessor
Pathogenic
M
MutationTaster
Benign
A;A
PROVEAN
Uncertain
D
Sift
Uncertain
D
Sift4G
Pathogenic
D
Polyphen
P
Vest4
MutPred
Loss of disorder (P = 0.0506);
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