4-64279754-ATT-AT

Variant names:

• chr4-64279754-AT-A
• rs11303004
• NM_001010874.5:c.*317delA

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001010874.5(TECRL):​c.*317delA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.97 (70650 hom., cov: 0)
  • Exomes 𝑓: 0.94 (307762 hom.)
• Consequence: TECRL NM_001010874.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.272
• Publications: 1 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: Labcorp Genetics (formerly Invitae), G2P, Genomics England PanelApp, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 4-64279754-AT-A is Benign according to our data. Variant chr4-64279754-AT-A is described in ClinVar as Benign. ClinVar VariationId is 1247451.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.975 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.*317delA		3_prime_UTR	Exon 12 of 12	NP_001010874.2
	TECRL	NM_001363796.1		c.964+1286delA		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.*317delA		3_prime_UTR	Exon 12 of 12	ENSP00000370607.3	Q5HYJ1
	TECRL	ENST00000941916.1		c.*317delA		3_prime_UTR	Exon 13 of 13	ENSP00000611975.1
	TECRL	ENST00000941915.1		c.*317delA		3_prime_UTR	Exon 13 of 13	ENSP00000611974.1

Frequencies

GnomAD3 genomes AF: 0.966 AC: 146119 AN: 151196 Hom.: 70620 Cov.: 0

Gnomad AFR AF: 0.944

Gnomad AMI AF: 0.916

Gnomad AMR AF: 0.977

Gnomad ASJ AF: 0.965

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.987

Gnomad FIN AF: 0.985

Gnomad MID AF: 0.984

Gnomad NFE AF: 0.971

Gnomad OTH AF: 0.964

GnomAD4 exome AF: 0.935 AC: 660746 AN: 706558 Hom.: 307762 Cov.: 0 AF XY: 0.935 AC XY: 306117 AN XY: 327290

African (AFR) AF: 0.903 AC: 12286 AN: 13612

American (AMR) AF: 0.947 AC: 881 AN: 930

Ashkenazi Jewish (ASJ) AF: 0.925 AC: 4194 AN: 4532

East Asian (EAS) AF: 0.954 AC: 3120 AN: 3270

South Asian (SAS) AF: 0.950 AC: 13186 AN: 13876

European-Finnish (FIN) AF: 0.948 AC: 379 AN: 400

Middle Eastern (MID) AF: 0.936 AC: 1280 AN: 1368

European-Non Finnish (NFE) AF: 0.935 AC: 603671 AN: 645340

Other (OTH) AF: 0.936 AC: 21749 AN: 23230

GnomAD4 genome AF: 0.966 AC: 146204 AN: 151304 Hom.: 70650 Cov.: 0 AF XY: 0.967 AC XY: 71455 AN XY: 73912

African (AFR) AF: 0.944 AC: 39020 AN: 41336

American (AMR) AF: 0.977 AC: 14851 AN: 15194

Ashkenazi Jewish (ASJ) AF: 0.965 AC: 3332 AN: 3454

East Asian (EAS) AF: 0.998 AC: 5145 AN: 5154

South Asian (SAS) AF: 0.987 AC: 4739 AN: 4802

European-Finnish (FIN) AF: 0.985 AC: 10186 AN: 10342

Middle Eastern (MID) AF: 0.983 AC: 285 AN: 290

European-Non Finnish (NFE) AF: 0.971 AC: 65784 AN: 67720

Other (OTH) AF: 0.965 AC: 2030 AN: 2104

Alfa AF: 0.964 Hom.: 2091

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.27
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: rs11303004; hg19: chr4-65145472; COSMIC: COSV67085270; COSMIC: COSV67085270;