chr4-64309896-C-T
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PM2PP3_ModeratePP5_Very_Strong
The NM_001010874.5(TECRL):c.587G>A(p.Arg196Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000248 in 1,611,646 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 Likely pathogenic (★★).
Frequency
Consequence
NM_001010874.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TECRL | ENST00000381210.8 | c.587G>A | p.Arg196Gln | missense_variant | Exon 6 of 12 | 1 | NM_001010874.5 | ENSP00000370607.3 | ||
TECRL | ENST00000511356.1 | n.692G>A | non_coding_transcript_exon_variant | Exon 6 of 7 | 1 | |||||
TECRL | ENST00000507440.5 | c.587G>A | p.Arg196Gln | missense_variant | Exon 6 of 12 | 5 | ENSP00000426043.1 | |||
TECRL | ENST00000513125.5 | n.160G>A | non_coding_transcript_exon_variant | Exon 3 of 6 | 5 |
Frequencies
GnomAD3 genomes AF: 0.0000198 AC: 3AN: 151824Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000240 AC: 6AN: 250378Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135376
GnomAD4 exome AF: 0.0000253 AC: 37AN: 1459822Hom.: 0 Cov.: 29 AF XY: 0.0000179 AC XY: 13AN XY: 726372
GnomAD4 genome AF: 0.0000198 AC: 3AN: 151824Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74130
ClinVar
Submissions by phenotype
Catecholaminergic polymorphic ventricular tachycardia 3 Pathogenic:2
Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Likely Pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with catecholaminergic polymorphic ventricular tachycardia 3 (MIM#614021). (I) 0106 - This gene is associated with autosomal recessive disease. (I) 0115 - Variants in this gene are known to have variable expressivity. This gene has been described to be associated with overlapping clinical features of both long QT syndrome and CPVT (PMID: 27861123). (I) 0200 - Variant is predicted to result in a missense amino acid change from arginine to glutamine. (I) 0251 - This variant is heterozygous. (I) 0304 - Variant is present in gnomAD <0.01 for a recessive condition (v2: 7 heterozygotes, 0 homozygotes). (SP) 0309 - An alternative amino acid change at the same position has been observed in gnomAD (v2: 1 heterozygote, 0 homozygotes). (I) 0502 - Missense variant with conflicting in silico predictions and uninformative conservation. (I) 0604 - Variant is not located in an established domain, motif, hotspot or informative constraint region. (I) 0705 - No comparable missense variants have previous evidence for pathogenicity. (I) 0802 - This variant has moderate previous evidence of pathogenicity in unrelated individuals. It has been reported in one compound heterozygous individual with CPVT (PMID: 30790670), and two homozygous individuals who presented with cardiac arrest, stress-induced atrial and ventricular tachycardia, and QT prolongation upon adrenergic stimulation, and who were both diagnosed with long QT syndrome (PMID: 27861123). (SP) 0905 - No published segregation evidence has been identified for this variant. (I) 1007 - No published functional evidence has been identified for this variant. (I) 1102 - Strong phenotype match for this individual. (SP) 1206 - This variant has been shown to be paternally inherited. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign -
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Long QT syndrome Pathogenic:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at