4-64280091-A-T
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001010874.5(TECRL):c.1073T>A(p.Met358Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0000345 in 1,595,072 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000036 ( 0 hom. )
Consequence
TECRL
NM_001010874.5 missense
NM_001010874.5 missense
Scores
3
10
6
Clinical Significance
Conservation
PhyloP100: 5.48
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 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TECRL | NM_001010874.5 | c.1073T>A | p.Met358Lys | missense_variant | 12/12 | ENST00000381210.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TECRL | ENST00000381210.8 | c.1073T>A | p.Met358Lys | missense_variant | 12/12 | 1 | NM_001010874.5 | P1 | |
TECRL | ENST00000511997.1 | c.*88T>A | 3_prime_UTR_variant | 2/2 | 1 | ||||
TECRL | ENST00000507440.5 | c.964+950T>A | intron_variant | 5 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152030Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000170 AC: 4AN: 234914Hom.: 0 AF XY: 0.0000314 AC XY: 4AN XY: 127394
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GnomAD4 exome AF: 0.0000360 AC: 52AN: 1443042Hom.: 0 Cov.: 30 AF XY: 0.0000460 AC XY: 33AN XY: 717774
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GnomAD4 genome AF: 0.0000197 AC: 3AN: 152030Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74256
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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 | Aug 31, 2023 | The p.M358K variant (also known as c.1073T>A), located in coding exon 12 of the TECRL gene, results from a T to A substitution at nucleotide position 1073. The methionine at codon 358 is replaced by lysine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. 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
Pathogenic
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Benign
DEOGEN2
Uncertain
D
Eigen
Benign
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T
M_CAP
Benign
T
MetaRNN
Uncertain
D
MetaSVM
Benign
T
MutationAssessor
Uncertain
M
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D
REVEL
Uncertain
Sift
Pathogenic
D
Sift4G
Pathogenic
D
Polyphen
B
Vest4
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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Calibrated prediction
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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