chr4-64280151-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001010874.5(TECRL):ā€‹c.1013A>Cā€‹(p.Gln338Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000686 in 1,603,284 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000026 ( 0 hom., cov: 32)
Exomes š‘“: 0.0000048 ( 0 hom. )

Consequence

TECRL
NM_001010874.5 missense

Scores

4
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.45
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 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.32033873).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
TECRLNM_001010874.5 linkuse as main transcriptc.1013A>C p.Gln338Pro missense_variant 12/12 ENST00000381210.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
TECRLENST00000381210.8 linkuse as main transcriptc.1013A>C p.Gln338Pro missense_variant 12/121 NM_001010874.5 P1
TECRLENST00000511997.1 linkuse as main transcriptc.*28A>C 3_prime_UTR_variant 2/21
TECRLENST00000507440.5 linkuse as main transcriptc.964+890A>C intron_variant 5

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
152040
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000965
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000122
AC:
3
AN:
245108
Hom.:
0
AF XY:
0.0000150
AC XY:
2
AN XY:
133010
show subpopulations
Gnomad AFR exome
AF:
0.000192
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000482
AC:
7
AN:
1451244
Hom.:
0
Cov.:
31
AF XY:
0.00000416
AC XY:
3
AN XY:
721666
show subpopulations
Gnomad4 AFR exome
AF:
0.000182
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:
0.00
Gnomad4 OTH exome
AF:
0.0000167
GnomAD4 genome
AF:
0.0000263
AC:
4
AN:
152040
Hom.:
0
Cov.:
32
AF XY:
0.0000404
AC XY:
3
AN XY:
74268
show subpopulations
Gnomad4 AFR
AF:
0.0000965
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:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000133
Hom.:
0
Bravo
AF:
0.0000491
ExAC
AF:
0.0000165
AC:
2

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 GeneticsJul 17, 2022The p.Q338P variant (also known as c.1013A>C), located in coding exon 12 of the TECRL gene, results from an A to C substitution at nucleotide position 1013. The glutamine at codon 338 is replaced by proline, an amino acid with similar properties. This amino acid position is conserved. 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: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.49
BayesDel_addAF
Benign
-0.23
T
BayesDel_noAF
Benign
-0.29
CADD
Benign
22
DANN
Uncertain
0.98
DEOGEN2
Uncertain
0.51
D
Eigen
Benign
0.0083
Eigen_PC
Benign
0.071
FATHMM_MKL
Uncertain
0.83
D
LIST_S2
Benign
0.75
T
M_CAP
Benign
0.014
T
MetaRNN
Benign
0.32
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.9
L
MutationTaster
Benign
0.82
D;D
PrimateAI
Benign
0.33
T
PROVEAN
Benign
-1.9
N
REVEL
Benign
0.18
Sift
Benign
0.19
T
Sift4G
Benign
0.13
T
Polyphen
0.49
P
Vest4
0.52
MVP
0.37
MPC
0.042
ClinPred
0.22
T
GERP RS
3.9
Varity_R
0.29
gMVP
0.86

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
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: rs758477637; hg19: chr4-65145869; API