chr6-123269854-G-T
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_006073.4(TRDN):c.1733C>A(p.Pro578Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000348 in 1,610,408 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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 Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TRDN | NM_006073.4 | c.1733C>A | p.Pro578Gln | missense_variant | 31/41 | ENST00000334268.9 | NP_006064.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TRDN | ENST00000334268.9 | c.1733C>A | p.Pro578Gln | missense_variant | 31/41 | 1 | NM_006073.4 | ENSP00000333984 | A2 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 151884Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000325 AC: 8AN: 246374Hom.: 0 AF XY: 0.0000224 AC XY: 3AN XY: 133654
GnomAD4 exome AF: 0.0000357 AC: 52AN: 1458524Hom.: 0 Cov.: 30 AF XY: 0.0000400 AC XY: 29AN XY: 725420
GnomAD4 genome AF: 0.0000263 AC: 4AN: 151884Hom.: 0 Cov.: 32 AF XY: 0.0000270 AC XY: 2AN XY: 74160
ClinVar
Submissions by phenotype
Catecholaminergic polymorphic ventricular tachycardia 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jul 26, 2022 | This sequence change replaces proline, which is neutral and non-polar, with glutamine, which is neutral and polar, at codon 578 of the TRDN protein (p.Pro578Gln). This variant is present in population databases (rs761240477, gnomAD 0.007%). 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: 532338). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The glutamine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect 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 | Jan 31, 2024 | The c.1733C>A (p.P578Q) alteration is located in exon 31 (coding exon 31) of the TRDN gene. This alteration results from a C to A substitution at nucleotide position 1733, causing the proline (P) at amino acid position 578 to be replaced by a glutamine (Q). 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