6-123571028-T-C
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_006073.4(TRDN):c.127A>G(p.Thr43Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000607 in 1,613,890 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 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. T43M) has been classified 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 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TRDN | NM_006073.4 | c.127A>G | p.Thr43Ala | missense_variant | 2/41 | ENST00000334268.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TRDN | ENST00000334268.9 | c.127A>G | p.Thr43Ala | missense_variant | 2/41 | 1 | NM_006073.4 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152210Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000161 AC: 4AN: 249166Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135172
GnomAD4 exome AF: 0.0000650 AC: 95AN: 1461680Hom.: 0 Cov.: 31 AF XY: 0.0000536 AC XY: 39AN XY: 727128
GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152210Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74348
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 | Nov 02, 2021 | - - |
Catecholaminergic polymorphic ventricular tachycardia 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 24, 2021 | This sequence change replaces threonine with alanine at codon 43 of the TRDN protein (p.Thr43Ala). The threonine residue is moderately conserved and there is a small physicochemical difference between threonine and alanine. This variant is present in population databases (rs367564871, ExAC 0.004%). This variant has not been reported in the literature in individuals affected with TRDN-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Not Available"; Align-GVGD: "Class C0"). 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 29, 2024 | The c.127A>G (p.T43A) alteration is located in exon 2 (coding exon 2) of the TRDN gene. This alteration results from a A to G substitution at nucleotide position 127, causing the threonine (T) at amino acid position 43 to be replaced by an alanine (A). 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