rs397516910
Positions:
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_001127453.2(GSDME):c.1183+9A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00101 in 1,614,186 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00046 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0011 ( 16 hom. )
Consequence
GSDME
NM_001127453.2 intron
NM_001127453.2 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.358
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 -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.79).
BP6
?
Variant 7-24706175-T-A is Benign according to our data. Variant chr7-24706175-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 44838.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
?
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00046 (70/152338) while in subpopulation SAS AF= 0.0101 (49/4830). AF 95% confidence interval is 0.00788. There are 0 homozygotes in gnomad4. There are 44 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
High AC in GnomAd4 at 70 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GSDME | NM_001127453.2 | c.1183+9A>T | intron_variant | ENST00000645220.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GSDME | ENST00000645220.1 | c.1183+9A>T | intron_variant | NM_001127453.2 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000460 AC: 70AN: 152220Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.00191 AC: 481AN: 251242Hom.: 6 AF XY: 0.00275 AC XY: 374AN XY: 135856
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GnomAD4 exome AF: 0.00106 AC: 1554AN: 1461848Hom.: 16 Cov.: 31 AF XY: 0.00152 AC XY: 1106AN XY: 727228
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GnomAD4 genome ? AF: 0.000460 AC: 70AN: 152338Hom.: 0 Cov.: 33 AF XY: 0.000591 AC XY: 44AN XY: 74492
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Feb 06, 2018 | 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 | Jun 29, 2015 | 1183+9A>T in intron 8 of DFNA5: This variant is not expected to have clinical si gnificance because it has been identified in 1.3% (214/16490) of South Asian chr omosomes by the Exome Aggregation Consortium and it is not located within the sp lice consensus sequence (ExAC, http://exac.broadinstitute.org; dbSNP rs397516910 ). - |
Autosomal dominant nonsyndromic hearing loss 5 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | May 11, 2023 | - - |
GSDME-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Nov 07, 2019 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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