rs104894971
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Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM1PP3_StrongPP5
The NM_003140.3(SRY):c.53G>A(p.Ser18Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a pathogenic outcome for this variant. 11/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: 𝑓 0.0 ( 0 hom., 0 hem., cov: 0)
Exomes 𝑓: 0.000011 ( 0 hom. 4 hem. )
Failed GnomAD Quality Control
Consequence
SRY
NM_003140.3 missense
NM_003140.3 missense
Scores
2
1
12
Clinical Significance
Conservation
PhyloP100: 0.675
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 7 ACMG points.
PM1
In a chain Sex-determining region Y protein (size 203) in uniprot entity SRY_HUMAN there are 14 pathogenic changes around while only 0 benign (100%) in NM_003140.3
PP3
MetaRNN computational evidence supports a deleterious effect, 0.987
PP5
Variant Y-2787551-C-T is Pathogenic according to our data. Variant chrY-2787551-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 9754.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SRY | NM_003140.3 | c.53G>A | p.Ser18Asn | missense_variant | 1/1 | ENST00000383070.2 | NP_003131.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SRY | ENST00000383070.2 | c.53G>A | p.Ser18Asn | missense_variant | 1/1 | 6 | NM_003140.3 | ENSP00000372547.1 |
Frequencies
GnomAD3 genomes AF: 0.00 AC: 0AN: 33667Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0AN XY: 33667 FAILED QC
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GnomAD3 exomes AF: 0.0000443 AC: 3AN: 67792Hom.: 0 AF XY: 0.0000443 AC XY: 3AN XY: 67792
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GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000110 AC: 4AN: 363072Hom.: 0 Cov.: 15 AF XY: 0.0000110 AC XY: 4AN XY: 363072
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GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 33667Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0AN XY: 33667
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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 | May 01, 2000 | - - |
Computational scores
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Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
DEOGEN2
Benign
T
FATHMM_MKL
Benign
N
LIST_S2
Benign
T
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D
MetaSVM
Uncertain
T
MutationAssessor
Benign
L
PROVEAN
Benign
N
Sift
Benign
T
Sift4G
Benign
T
Polyphen
B
Vest4
MutPred
Loss of phosphorylation at S18 (P = 0.0666);
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at