rs61731036
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Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_001127453.2(GSDME):āc.1334T>Cā(p.Phe445Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000186 in 1,614,046 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: š 0.0000066 ( 0 hom., cov: 32)
Exomes š: 0.0000014 ( 0 hom. )
Consequence
GSDME
NM_001127453.2 missense
NM_001127453.2 missense
Scores
8
7
3
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 5.24
Genes affected
GSDME (HGNC:2810): (gasdermin E) Hearing impairment is a heterogeneous condition with over 40 loci described. The protein encoded by this gene is expressed in fetal cochlea, however, its function is not known. Nonsyndromic hearing impairment is associated with a mutation in this gene. Three transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.928
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
GSDME | NM_001127453.2 | c.1334T>C | p.Phe445Ser | missense_variant | 10/10 | ENST00000645220.1 | NP_001120925.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
GSDME | ENST00000645220.1 | c.1334T>C | p.Phe445Ser | missense_variant | 10/10 | NM_001127453.2 | ENSP00000494186.1 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152160Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251454Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135900
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GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461886Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 727244
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GnomAD4 genome AF: 0.00000657 AC: 1AN: 152160Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74332
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ClinVar
Not reported inComputational scores
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Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T;T;.;.;T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
.;.;.;T;T
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D;D;D;D
MetaSVM
Uncertain
D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;.;D;D;D
REVEL
Pathogenic
Sift
Uncertain
D;.;D;D;D
Sift4G
Pathogenic
D;.;D;D;D
Polyphen
D;D;.;.;D
Vest4
MutPred
Gain of disorder (P = 0.0038);Gain of disorder (P = 0.0038);.;.;Gain of disorder (P = 0.0038);
MVP
MPC
ClinPred
D
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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