rs374353052
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP3BS2
The NM_001127453.2(GSDME):c.1277_1279del(p.Asp426del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000295 in 1,613,480 control chromosomes in the GnomAD database, including 6 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. D426D) has been classified as Likely benign.
Frequency
Consequence
NM_001127453.2 inframe_deletion
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GSDME | NM_001127453.2 | c.1277_1279del | p.Asp426del | inframe_deletion | 10/10 | ENST00000645220.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GSDME | ENST00000645220.1 | c.1277_1279del | p.Asp426del | inframe_deletion | 10/10 | NM_001127453.2 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000223 AC: 34AN: 152200Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000684 AC: 172AN: 251364Hom.: 3 AF XY: 0.000802 AC XY: 109AN XY: 135850
GnomAD4 exome AF: 0.000302 AC: 442AN: 1461162Hom.: 6 AF XY: 0.000409 AC XY: 297AN XY: 726964
GnomAD4 genome AF: 0.000223 AC: 34AN: 152318Hom.: 0 Cov.: 32 AF XY: 0.000295 AC XY: 22AN XY: 74480
ClinVar
Submissions by phenotype
Autosomal dominant nonsyndromic hearing loss 5 Pathogenic:1
Likely pathogenic, criteria provided, single submitter | research | Santos-Cortez Lab, University of Colorado School of Medicine | Jan 17, 2019 | - - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jul 25, 2017 | p.Asp426del in exon 10 of DFNA5: This variant is not expected to have clinical s ignificance because it has been identified in 0.5% (158/30778) of South Asian ch romosomes including 3 homozygotes by the Genome Aggregation Database (gnomAD, ht tp://gnomad.broadinstitute.org; rs374353052). - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Oct 09, 2023 | - - |
GSDME-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Nov 13, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at