rs563042010

Variant names:

• chr4-64280180-C-A
• rs563042010
• ENST00000511997.1:c.83G>T

Your query was ambiguous. Multiple possible variants found:

• chr4-64280180-C-A
• chr4-64280180-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PM4

The ENST00000511997.1(TECRL):​c.83G>T​(p.Ter28Leuext*?) variant causes a stop lost change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000195 in 1,536,682 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: 0.0000014 (0 hom.)
• Consequence: TECRL ENST00000511997.1 stop_lost
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.28

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]

ACMG classification

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 27 codons.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TECRL	NM_001010874.5	c.984G>T	p.Leu328Leu	synonymous_variant	Exon 12 of 12	ENST00000381210.8	NP_001010874.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TECRL	ENST00000511997.1	c.83G>T	p.Ter28Leuext*?	stop_lost	Exon 2 of 2	1		ENSP00000423975.1
TECRL	ENST00000381210.8	c.984G>T	p.Leu328Leu	synonymous_variant	Exon 12 of 12	1	NM_001010874.5	ENSP00000370607.3
TECRL	ENST00000507440.5	c.964+861G>T		intron_variant	Intron 11 of 11	5		ENSP00000426043.1

Frequencies

GnomAD3 genomes AF: 0.00000659 AC: 1 AN: 151726 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

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

GnomAD4 exome AF: 0.00000144 AC: 2 AN: 1384838 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 686146

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.0000429

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: 0.0000176

GnomAD4 genome AF: 0.00000659 AC: 1 AN: 151844 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74202

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ExAC AF: 0.0000165 AC: 2

Asia WGS AF: 0.000291 AC: 1 AN: 3446

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Cardiovascular phenotype Uncertain:1

Jul 15, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.984G>T variant (also known as p.L328L), located in coding exon 12 of the TECRL gene, results from a G to T substitution at nucleotide position 984. This nucleotide substitution does not change the leucine at codon 328. This nucleotide position is not well conserved in available vertebrate species. In silico splice site analysis predicts that this alteration may weaken the native splice acceptor site. Based on the available evidence, the clinical significance of this variant remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.052	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	2.1
DANN	Benign	0.51
Eigen	Benign	0.025
Eigen_PC	Benign	0.049
FATHMM_MKL	Uncertain	0.76	D
GERP RS		2.4

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.27		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.27		Position offset: 19

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

Publications

LitVar

Other links and lift over

dbSNP: rs563042010; hg19: chr4-65145898;