4-64279745-G-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001010874.5(TECRL):​c.*327C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.973 in 981,498 control chromosomes in the GnomAD database, including 465,148 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.97 (71181 hom., cov: 31)
  • Exomes 𝑓: 0.97 (393967 hom.)
• Consequence: TECRL NM_001010874.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.05).
• BP6: Variant 4-64279745-G-T is Benign according to our data. Variant chr4-64279745-G-T is described in ClinVar as Benign. ClinVar VariationId is 1296724.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001010874.5. 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>A		3_prime_UTR	Exon 12 of 12	NP_001010874.2
	TECRL	NM_001363796.1		c.964+1296C>A		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>A		3_prime_UTR	Exon 12 of 12	ENSP00000370607.3	Q5HYJ1
	TECRL	ENST00000941916.1		c.*327C>A		3_prime_UTR	Exon 13 of 13	ENSP00000611975.1
	TECRL	ENST00000941915.1		c.*327C>A		3_prime_UTR	Exon 13 of 13	ENSP00000611974.1

Frequencies

GnomAD3 genomes AF: 0.968 AC: 147025 AN: 151960 Hom.: 71147 Cov.: 31

Gnomad AFR AF: 0.945

Gnomad AMI AF: 0.916

Gnomad AMR AF: 0.978

Gnomad ASJ AF: 0.965

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.989

Gnomad FIN AF: 0.988

Gnomad MID AF: 0.987

Gnomad NFE AF: 0.972

Gnomad OTH AF: 0.965

GnomAD4 exome AF: 0.975 AC: 808355 AN: 829420 Hom.: 393967 Cov.: 17 AF XY: 0.974 AC XY: 373880 AN XY: 383672

African (AFR) AF: 0.945 AC: 14859 AN: 15718

American (AMR) AF: 0.984 AC: 1053 AN: 1070

Ashkenazi Jewish (ASJ) AF: 0.966 AC: 5047 AN: 5226

East Asian (EAS) AF: 0.999 AC: 3744 AN: 3748

South Asian (SAS) AF: 0.989 AC: 16332 AN: 16516

European-Finnish (FIN) AF: 0.989 AC: 441 AN: 446

Middle Eastern (MID) AF: 0.973 AC: 1571 AN: 1614

European-Non Finnish (NFE) AF: 0.975 AC: 738657 AN: 757780

Other (OTH) AF: 0.976 AC: 26651 AN: 27302

GnomAD4 genome AF: 0.967 AC: 147118 AN: 152078 Hom.: 71181 Cov.: 31 AF XY: 0.968 AC XY: 71972 AN XY: 74360

African (AFR) AF: 0.945 AC: 39185 AN: 41470

American (AMR) AF: 0.978 AC: 14948 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.965 AC: 3351 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5166 AN: 5166

South Asian (SAS) AF: 0.989 AC: 4775 AN: 4830

European-Finnish (FIN) AF: 0.988 AC: 10429 AN: 10552

Middle Eastern (MID) AF: 0.986 AC: 290 AN: 294

European-Non Finnish (NFE) AF: 0.972 AC: 66101 AN: 67994

Other (OTH) AF: 0.965 AC: 2041 AN: 2114

Alfa AF: 0.962 Hom.: 16198

Bravo AF: 0.966

Asia WGS AF: 0.984 AC: 3416 AN: 3472

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.55
DANN	Benign	0.32
PhyloP100		-0.88
Mutation Taster		=100/0	polymorphism (auto)

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;