ENST00000381210:c.*327C>G

Variant names:

• chr4-64279745-G-C
• rs2348313
• NM_001010874.5:c.*327C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000381210.8(TECRL):​c.*327C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TECRL ENST00000381210.8 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.878
• Publications: 2 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000381210.8. 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.*327C>G		3_prime_UTR	Exon 12 of 12	NP_001010874.2
	TECRL	NM_001363796.1		c.964+1296C>G		intron	N/A	NP_001350725.1	E9PD39

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TECRL	ENST00000381210.8	TSL:1 MANE Select	c.*327C>G		3_prime_UTR	Exon 12 of 12	ENSP00000370607.3	Q5HYJ1
	TECRL	ENST00000941916.1		c.*327C>G		3_prime_UTR	Exon 13 of 13	ENSP00000611975.1
	TECRL	ENST00000941915.1		c.*327C>G		3_prime_UTR	Exon 13 of 13	ENSP00000611974.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 829472 Hom.: 0 Cov.: 17 AF XY: 0.00 AC XY: 0 AN XY: 383690

African (AFR) AF: 0.00 AC: 0 AN: 15720

American (AMR) AF: 0.00 AC: 0 AN: 1070

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 5226

East Asian (EAS) AF: 0.00 AC: 0 AN: 3748

South Asian (SAS) AF: 0.00 AC: 0 AN: 16520

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 446

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1618

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 757822

Other (OTH) AF: 0.00 AC: 0 AN: 27302

GnomAD4 genome Cov.: 31

Alfa AF: 0.0000286 Hom.: 16198

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.52
DANN	Benign	0.19
PhyloP100		-0.88

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

Other links and lift over

dbSNP: rs2348313; hg19: chr4-65145463;