7-24702804-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001127453.2(GSDME):​c.1213G>C​(p.Gly405Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,300 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G405S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)
Exomes š‘“: 6.8e-7 ( 0 hom. )

Consequence

GSDME
NM_001127453.2 missense

Scores

2
16

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.769
Variant links:
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 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GSDMENM_001127453.2 linkc.1213G>C p.Gly405Arg missense_variant Exon 9 of 10 ENST00000645220.1 NP_001120925.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GSDMEENST00000645220.1 linkc.1213G>C p.Gly405Arg missense_variant Exon 9 of 10 NM_001127453.2 ENSP00000494186.1 O60443-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461300
Hom.:
0
Cov.:
30
AF XY:
0.00
AC XY:
0
AN XY:
726942
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.00e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.49
BayesDel_addAF
Benign
-0.11
T
BayesDel_noAF
Benign
-0.40
CADD
Benign
19
DANN
Benign
0.84
DEOGEN2
Benign
0.053
T;T;.;.;T;.
Eigen
Benign
-0.16
Eigen_PC
Benign
-0.026
FATHMM_MKL
Benign
0.67
D
LIST_S2
Benign
0.77
.;.;.;T;T;T
M_CAP
Benign
0.011
T
MetaRNN
Uncertain
0.53
D;D;D;D;D;D
MetaSVM
Benign
-1.1
T
PrimateAI
Benign
0.46
T
PROVEAN
Benign
-1.4
N;.;D;D;N;D
REVEL
Benign
0.17
Sift
Benign
0.27
T;.;T;T;T;D
Sift4G
Benign
0.69
T;.;T;T;T;D
Polyphen
0.32
B;B;.;.;B;.
Vest4
0.36
MutPred
0.79
Loss of ubiquitination at K409 (P = 0.0362);Loss of ubiquitination at K409 (P = 0.0362);.;.;Loss of ubiquitination at K409 (P = 0.0362);.;
MVP
0.24
MPC
0.080
ClinPred
0.56
D
GERP RS
4.9
Varity_R
0.066
gMVP
0.42

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-24742423; API