4-64280166-A-T
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_001010874.5(TECRL):c.998T>A(p.Met333Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0000257 in 1,597,722 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. M333T) has been classified as Uncertain significance.
Frequency
Consequence
NM_001010874.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TECRL | NM_001010874.5 | c.998T>A | p.Met333Lys | missense_variant | 12/12 | ENST00000381210.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TECRL | ENST00000381210.8 | c.998T>A | p.Met333Lys | missense_variant | 12/12 | 1 | NM_001010874.5 | P1 | |
TECRL | ENST00000511997.1 | c.*13T>A | 3_prime_UTR_variant | 2/2 | 1 | ||||
TECRL | ENST00000507440.5 | c.964+875T>A | intron_variant | 5 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152076Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000248 AC: 6AN: 241736Hom.: 0 AF XY: 0.0000305 AC XY: 4AN XY: 131278
GnomAD4 exome AF: 0.0000256 AC: 37AN: 1445646Hom.: 0 Cov.: 30 AF XY: 0.0000390 AC XY: 28AN XY: 718780
GnomAD4 genome AF: 0.0000263 AC: 4AN: 152076Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74282
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Oct 04, 2022 | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 29, 2022 | The p.M333K variant (also known as c.998T>A), located in coding exon 12 of the TECRL gene, results from a T to A substitution at nucleotide position 998. The methionine at codon 333 is replaced by lysine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious 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