rs200953683
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_006073.4(TRDN):c.419A>G(p.Lys140Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00017 in 1,462,624 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_006073.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TRDN | NM_006073.4 | c.419A>G | p.Lys140Arg | missense_variant | 4/41 | ENST00000334268.9 | |
LOC105377982 | XR_001743833.2 | n.2346-6011T>C | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TRDN | ENST00000334268.9 | c.419A>G | p.Lys140Arg | missense_variant | 4/41 | 1 | NM_006073.4 | A2 | |
ENST00000648704.1 | n.449-6077T>C | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.000171 AC: 26AN: 152024Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000205 AC: 23AN: 112082Hom.: 0 AF XY: 0.000251 AC XY: 15AN XY: 59668
GnomAD4 exome AF: 0.000169 AC: 222AN: 1310482Hom.: 0 Cov.: 25 AF XY: 0.000191 AC XY: 123AN XY: 645044
GnomAD4 genome ? AF: 0.000171 AC: 26AN: 152142Hom.: 0 Cov.: 32 AF XY: 0.000161 AC XY: 12AN XY: 74416
ClinVar
Submissions by phenotype
Catecholaminergic polymorphic ventricular tachycardia 1;C3809536:Catecholaminergic polymorphic ventricular tachycardia 5 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Sep 16, 2021 | - - |
Catecholaminergic polymorphic ventricular tachycardia 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 23, 2022 | This sequence change replaces lysine, which is basic and polar, with arginine, which is basic and polar, at codon 140 of the TRDN protein (p.Lys140Arg). This variant is present in population databases (rs200953683, gnomAD 0.07%). This variant has not been reported in the literature in individuals affected with TRDN-related conditions. ClinVar contains an entry for this variant (Variation ID: 408730). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt TRDN protein function. 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. - |
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 25, 2022 | The p.K140R variant (also known as c.419A>G), located in coding exon 4 of the TRDN gene, results from an A to G substitution at nucleotide position 419. The lysine at codon 140 is replaced by arginine, an amino acid with highly similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. 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