chr4-64281065-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_001010874.5(TECRL):ā€‹c.940A>Cā€‹(p.Thr314Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000936 in 1,603,058 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 (ā˜…).

Frequency

Genomes: š‘“ 0.0000066 ( 0 hom., cov: 33)
Exomes š‘“: 0.0000096 ( 0 hom. )

Consequence

TECRL
NM_001010874.5 missense

Scores

3
12
4

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.23
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.836

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
TECRLNM_001010874.5 linkuse as main transcriptc.940A>C p.Thr314Pro missense_variant 11/12 ENST00000381210.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
TECRLENST00000381210.8 linkuse as main transcriptc.940A>C p.Thr314Pro missense_variant 11/121 NM_001010874.5 P1
TECRLENST00000511997.1 linkuse as main transcriptc.63+409A>C intron_variant 1
TECRLENST00000507440.5 linkuse as main transcriptc.940A>C p.Thr314Pro missense_variant 11/125

Frequencies

GnomAD3 genomes
AF:
0.00000658
AC:
1
AN:
152020
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000965
AC:
14
AN:
1451038
Hom.:
0
Cov.:
29
AF XY:
0.00000831
AC XY:
6
AN XY:
721900
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000127
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000658
AC:
1
AN:
152020
Hom.:
0
Cov.:
33
AF XY:
0.0000135
AC XY:
1
AN XY:
74246
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000565
Hom.:
0
Bravo
AF:
0.00000756

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 submitterclinical testingAmbry GeneticsMay 03, 2024The p.T314P variant (also known as c.940A>C), located in coding exon 11 of the TECRL gene, results from an A to C substitution at nucleotide position 940. The threonine at codon 314 is replaced by proline, an amino acid with highly similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this variant remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.78
BayesDel_addAF
Uncertain
0.077
D
BayesDel_noAF
Benign
-0.13
CADD
Pathogenic
26
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.71
.;D
Eigen
Uncertain
0.57
Eigen_PC
Uncertain
0.52
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Uncertain
0.86
D;T
M_CAP
Benign
0.037
D
MetaRNN
Pathogenic
0.84
D;D
MetaSVM
Benign
-0.82
T
MutationAssessor
Pathogenic
3.0
.;M
MutationTaster
Benign
1.0
D;D
PrimateAI
Uncertain
0.69
T
PROVEAN
Uncertain
-3.2
D;D
REVEL
Uncertain
0.40
Sift
Uncertain
0.0030
D;D
Sift4G
Uncertain
0.030
D;D
Polyphen
1.0
.;D
Vest4
0.72
MutPred
0.76
Loss of stability (P = 0.1242);Loss of stability (P = 0.1242);
MVP
0.48
MPC
0.084
ClinPred
0.99
D
GERP RS
4.7
Varity_R
0.81
gMVP
0.87

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.18
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1359562110; hg19: chr4-65146783; API