4-64280180-C-G

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PM4

The ENST00000511997.1(TECRL):​c.83G>C​(p.Ter28Serext*?) variant causes a stop lost change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000722 in 1,384,842 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: TECRL ENST00000511997.1 stop_lost
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.28
• Publications: 0 publications found

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]

TECRL Gene-Disease associations (from GenCC):

• catecholaminergic polymorphic ventricular tachycardia

  Inheritance: AD, AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
• catecholaminergic polymorphic ventricular tachycardia 3

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, LIMITED Submitted by: PanelApp Australia, Genomics England PanelApp, G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000511997.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TECRL	NM_001010874.5	MANE Select	c.984G>C	p.Leu328Leu	synonymous	Exon 12 of 12	NP_001010874.2
	TECRL	NM_001363796.1		c.964+861G>C		intron	N/A	NP_001350725.1	E9PD39

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TECRL	ENST00000511997.1	TSL:1	c.83G>C	p.Ter28Serext*?	stop_lost	Exon 2 of 2	ENSP00000423975.1	H0Y9F0
	TECRL	ENST00000381210.8	TSL:1 MANE Select	c.984G>C	p.Leu328Leu	synonymous	Exon 12 of 12	ENSP00000370607.3	Q5HYJ1
	TECRL	ENST00000941916.1		c.1209G>C	p.Leu403Leu	synonymous	Exon 13 of 13	ENSP00000611975.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.22e-7 AC: 1 AN: 1384842 Hom.: 0 Cov.: 30 AF XY: 0.00000146 AC XY: 1 AN XY: 686148

African (AFR) AF: 0.00 AC: 0 AN: 30116

American (AMR) AF: 0.00 AC: 0 AN: 31712

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23310

East Asian (EAS) AF: 0.00 AC: 0 AN: 37754

South Asian (SAS) AF: 0.00 AC: 0 AN: 70930

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51176

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5430

European-Non Finnish (NFE) AF: 9.28e-7 AC: 1 AN: 1077672

Other (OTH) AF: 0.00 AC: 0 AN: 56742

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	3.2
DANN	Benign	0.59
Eigen	Benign	0.025
Eigen_PC	Benign	0.049
FATHMM_MKL	Uncertain	0.79	D
PhyloP100		1.3
GERP RS		2.4
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs563042010; hg19: chr4-65145898;