rs765449931
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.
The NM_017636.4(TRPM4):c.3386A>T(p.Lys1129Met) variant causes a missense change. The variant allele was found at a frequency of 0.0000558 in 1,613,992 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. K1129N) has been classified as Uncertain significance.
Frequency
Consequence
NM_017636.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TRPM4 | NM_017636.4 | c.3386A>T | p.Lys1129Met | missense_variant | 22/25 | ENST00000252826.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TRPM4 | ENST00000252826.10 | c.3386A>T | p.Lys1129Met | missense_variant | 22/25 | 1 | NM_017636.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152214Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000160 AC: 4AN: 250464Hom.: 0 AF XY: 0.00000738 AC XY: 1AN XY: 135418
GnomAD4 exome AF: 0.0000588 AC: 86AN: 1461778Hom.: 0 Cov.: 34 AF XY: 0.0000536 AC XY: 39AN XY: 727180
GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152214Hom.: 0 Cov.: 31 AF XY: 0.0000269 AC XY: 2AN XY: 74368
ClinVar
Submissions by phenotype
Progressive familial heart block type IB Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 25, 2023 | This variant has not been reported in the literature in individuals affected with TRPM4-related conditions. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 536797). This variant is present in population databases (rs765449931, gnomAD 0.004%). This sequence change replaces lysine, which is basic and polar, with methionine, which is neutral and non-polar, at codon 1129 of the TRPM4 protein (p.Lys1129Met). - |
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 25, 2022 | The p.K1129M variant (also known as c.3386A>T), located in coding exon 22 of the TRPM4 gene, results from an A to T substitution at nucleotide position 3386. The lysine at codon 1129 is replaced by methionine, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at