rs1013171855
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_017636.4(TRPM4):c.2863C>T(p.Arg955Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000558 in 1,613,930 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_017636.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TRPM4 | NM_017636.4 | c.2863C>T | p.Arg955Trp | missense_variant | 19/25 | ENST00000252826.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TRPM4 | ENST00000252826.10 | c.2863C>T | p.Arg955Trp | missense_variant | 19/25 | 1 | NM_017636.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152128Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251006Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135796
GnomAD4 exome AF: 0.00000479 AC: 7AN: 1461802Hom.: 0 Cov.: 34 AF XY: 0.00000550 AC XY: 4AN XY: 727206
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152128Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1AN XY: 74312
ClinVar
Submissions by phenotype
Progressive familial heart block type IB Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 04, 2016 | In summary, this variant is a novel missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a TRPM4-related disease. This sequence change replaces arginine with tryptophan at codon 955 of the TRPM4 protein (p.Arg955Trp). The arginine residue is weakly conserved and there is a moderate physicochemical difference between arginine and tryptophan. - |
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 13, 2023 | The c.2863C>T (p.R955W) alteration is located in exon 19 (coding exon 19) of the TRPM4 gene. This alteration results from a C to T substitution at nucleotide position 2863, causing the arginine (R) at amino acid position 955 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at