rs765535147
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP6BS2
The NM_017636.4(TRPM4):c.2987_3014del(p.Glu996GlyfsTer118) variant causes a frameshift change. The variant allele was found at a frequency of 0.0000837 in 1,613,806 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. S995S) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_017636.4 frameshift
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 |
---|---|---|---|---|---|---|---|
TRPM4 | NM_017636.4 | c.2987_3014del | p.Glu996GlyfsTer118 | frameshift_variant | 20/25 | ENST00000252826.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TRPM4 | ENST00000252826.10 | c.2987_3014del | p.Glu996GlyfsTer118 | frameshift_variant | 20/25 | 1 | NM_017636.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000657 AC: 10AN: 152178Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000164 AC: 41AN: 250516Hom.: 0 AF XY: 0.000177 AC XY: 24AN XY: 135508
GnomAD4 exome AF: 0.0000855 AC: 125AN: 1461510Hom.: 1 AF XY: 0.0000894 AC XY: 65AN XY: 727078
GnomAD4 genome ? AF: 0.0000657 AC: 10AN: 152296Hom.: 0 Cov.: 32 AF XY: 0.0000940 AC XY: 7AN XY: 74460
ClinVar
Submissions by phenotype
Progressive familial heart block type IB Uncertain:1Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Nov 23, 2021 | - - |
Uncertain significance, criteria provided, single submitter | reference population | Soonchunhyang University Bucheon Hospital, Soonchunhyang University Medical Center | Mar 18, 2016 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Feb 01, 2023 | Reported in an individual with DCM and sick sinus syndrome and in an individual with atrioventricular nodal reentry tachycardia; described as c.2985_3012del in both cases (Li et al., 2020; Luo et al., 2020); Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene or region of a gene for which loss of function is not a well-established mechanism of disease; This variant is associated with the following publications: (PMID: 32508047, 31521807) - |
Cardiovascular phenotype Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 26, 2019 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at