rs758488919
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Uncertain significance. The variant received 4 ACMG points: 8P and 4B. PVS1BS2
The NM_001127453.2(GSDME):c.116_119delAAAA(p.Lys39ArgfsTer24) variant causes a frameshift change. The variant allele was found at a frequency of 0.00000434 in 1,614,062 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000041 ( 0 hom. )
Consequence
GSDME
NM_001127453.2 frameshift
NM_001127453.2 frameshift
Scores
Not classified
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 6.78
Publications
2 publications found
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]
GSDME Gene-Disease associations (from GenCC):
- autosomal dominant nonsyndromic hearing lossInheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
- autosomal dominant nonsyndromic hearing loss 5Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
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ACMG classification
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 4 ACMG points.
PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
BS2
High AC in GnomAdExome4 at 6 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
GSDME | NM_001127453.2 | c.116_119delAAAA | p.Lys39ArgfsTer24 | frameshift_variant | Exon 2 of 10 | ENST00000645220.1 | NP_001120925.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152160Hom.: 0 Cov.: 32 show subpopulations
GnomAD3 genomes
AF:
AC:
1
AN:
152160
Hom.:
Cov.:
32
Gnomad AFR
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GnomAD2 exomes AF: 0.0000119 AC: 3AN: 251436 AF XY: 0.0000147 show subpopulations
GnomAD2 exomes
AF:
AC:
3
AN:
251436
AF XY:
Gnomad AFR exome
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GnomAD4 exome AF: 0.00000410 AC: 6AN: 1461784Hom.: 0 AF XY: 0.00000413 AC XY: 3AN XY: 727200 show subpopulations
GnomAD4 exome
AF:
AC:
6
AN:
1461784
Hom.:
AF XY:
AC XY:
3
AN XY:
727200
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33480
American (AMR)
AF:
AC:
0
AN:
44724
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26134
East Asian (EAS)
AF:
AC:
0
AN:
39698
South Asian (SAS)
AF:
AC:
1
AN:
86258
European-Finnish (FIN)
AF:
AC:
0
AN:
53388
Middle Eastern (MID)
AF:
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
AC:
4
AN:
1111938
Other (OTH)
AF:
AC:
1
AN:
60396
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.425
Heterozygous variant carriers
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Allele balance
Age Distribution
Exome Het
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Age
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152278Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74460 show subpopulations
GnomAD4 genome
AF:
AC:
1
AN:
152278
Hom.:
Cov.:
32
AF XY:
AC XY:
0
AN XY:
74460
show subpopulations
African (AFR)
AF:
AC:
0
AN:
41574
American (AMR)
AF:
AC:
0
AN:
15286
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3468
East Asian (EAS)
AF:
AC:
1
AN:
5190
South Asian (SAS)
AF:
AC:
0
AN:
4820
European-Finnish (FIN)
AF:
AC:
0
AN:
10606
Middle Eastern (MID)
AF:
AC:
0
AN:
294
European-Non Finnish (NFE)
AF:
AC:
0
AN:
68014
Other (OTH)
AF:
AC:
0
AN:
2114
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.575
Heterozygous variant carriers
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Allele balance
EpiCase
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EpiControl
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ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
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Prediction
PhyloP100
Splicing
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Calibrated prediction
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Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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