chr4-64280179-T-A
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Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PM4
The ENST00000511997.1(TECRL):c.84A>T(p.Ter28CysextTer1) variant causes a stop lost change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000013 in 1,539,946 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 7.2e-7 ( 0 hom. )
Consequence
TECRL
ENST00000511997.1 stop_lost
ENST00000511997.1 stop_lost
Scores
2
16
Clinical Significance
Conservation
PhyloP100: 1.42
Genes affected
TECRL (HGNC:27365): (trans-2,3-enoyl-CoA reductase like) The protein encoded by this gene contains a ubiquitin-like domain in the N-terminal region, three transmembrane segments and a C-terminal 3-oxo-5-alpha steroid 4-dehydrogenase domain. The protein belongs to the steroid 5-alpha reductase family. Mutations in this gene result in ventricular tachycardia, catecholaminergic polymorphic, 3. [provided by RefSeq, Apr 2017]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PM4
Stoplost variant in ENST00000511997.1 Downstream stopcodon found after 6 codons.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TECRL | NM_001010874.5 | c.985A>T | p.Met329Leu | missense_variant | 12/12 | ENST00000381210.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TECRL | ENST00000511997.1 | c.84A>T | p.Ter28CysextTer1 | stop_lost | 2/2 | 1 | |||
TECRL | ENST00000381210.8 | c.985A>T | p.Met329Leu | missense_variant | 12/12 | 1 | NM_001010874.5 | P1 | |
TECRL | ENST00000507440.5 | c.964+862A>T | intron_variant | 5 |
Frequencies
GnomAD3 genomes AF: 0.00000658 AC: 1AN: 151994Hom.: 0 Cov.: 32
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GnomAD4 exome AF: 7.20e-7 AC: 1AN: 1387952Hom.: 0 Cov.: 30 AF XY: 0.00000145 AC XY: 1AN XY: 687764
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GnomAD4 genome AF: 0.00000658 AC: 1AN: 151994Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74226
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 16, 2020 | The p.M329L variant (also known as c.985A>T), located in coding exon 12 of the TECRL gene, results from an A to T substitution at nucleotide position 985. The methionine at codon 329 is replaced by leucine, an amino acid with highly similar properties. This amino acid position is well conserved in available vertebrate species; however, leucine is the reference amino acid in other 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:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
D
LIST_S2
Benign
T
M_CAP
Benign
D
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationTaster
Benign
D;N
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
D
Sift4G
Uncertain
D
Polyphen
B
Vest4
MutPred
Gain of catalytic residue at M329 (P = 0.0098);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at