rs17149912
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_001127453.2(GSDME):āc.1200A>Gā(p.Ala400=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.166 in 1,612,490 control chromosomes in the GnomAD database, including 24,394 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ā ).
Frequency
Genomes: š 0.17 ( 2310 hom., cov: 33)
Exomes š: 0.17 ( 22084 hom. )
Consequence
GSDME
NM_001127453.2 synonymous
NM_001127453.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.285
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 Benign. Variant got -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.86).
BP6
?
Variant 7-24702817-T-C is Benign according to our data. Variant chr7-24702817-T-C is described in ClinVar as [Benign]. Clinvar id is 44840.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-0.285 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.255 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GSDME | NM_001127453.2 | c.1200A>G | p.Ala400= | synonymous_variant | 9/10 | ENST00000645220.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GSDME | ENST00000645220.1 | c.1200A>G | p.Ala400= | synonymous_variant | 9/10 | NM_001127453.2 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.168 AC: 25534AN: 152104Hom.: 2312 Cov.: 33
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GnomAD3 exomes AF: 0.201 AC: 50594AN: 251402Hom.: 5793 AF XY: 0.197 AC XY: 26822AN XY: 135878
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GnomAD4 exome AF: 0.166 AC: 242933AN: 1460268Hom.: 22084 Cov.: 31 AF XY: 0.169 AC XY: 122671AN XY: 726456
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GnomAD4 genome ? AF: 0.168 AC: 25539AN: 152222Hom.: 2310 Cov.: 33 AF XY: 0.176 AC XY: 13098AN XY: 74416
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ClinVar
Significance: Benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | May 09, 2017 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | May 07, 2012 | Ala400Ala in Exon 09 of DFNA5: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue, is not located withi n the splice consensus sequence, and has been identified in 15.6% (1098/7020) of European American chromosomes from a broad population by the NHLBI Exome Sequen cing Project (http://evs.gs.washington.edu/EVS; dbSNP rs17149912). - |
Autosomal dominant nonsyndromic hearing loss 5 Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at