4-64279754-ATT-ATTT

Variant names:

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

Variant summary

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

The NM_001010874.5(TECRL):​c.*317dupA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000040 (0 hom., cov: 0)
  • Exomes 𝑓: 0.000051 (0 hom.)
• Consequence: TECRL NM_001010874.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• 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: Uncertain_significance. The variant received 0 ACMG points.

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.*317dupA		3_prime_UTR	Exon 12 of 12	NP_001010874.2
	TECRL	NM_001363796.1		c.964+1286dupA		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.*317dupA		3_prime_UTR	Exon 12 of 12	ENSP00000370607.3	Q5HYJ1
	TECRL	ENST00000941916.1		c.*317dupA		3_prime_UTR	Exon 13 of 13	ENSP00000611975.1
	TECRL	ENST00000941915.1		c.*317dupA		3_prime_UTR	Exon 13 of 13	ENSP00000611974.1

Frequencies

GnomAD3 genomes AF: 0.0000331 AC: 5 AN: 151206 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000485

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000295

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000510 AC: 36 AN: 706558 Hom.: 0 Cov.: 0 AF XY: 0.0000611 AC XY: 20 AN XY: 327302

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000661 AC: 9 AN: 13618

American (AMR) AF: 0.00 AC: 0 AN: 930

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 4532

East Asian (EAS) AF: 0.00 AC: 0 AN: 3272

South Asian (SAS) AF: 0.0000721 AC: 1 AN: 13876

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 400

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1370

European-Non Finnish (NFE) AF: 0.0000387 AC: 25 AN: 645328

Other (OTH) AF: 0.0000430 AC: 1 AN: 23232

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0000397 AC: 6 AN: 151314 Hom.: 0 Cov.: 0 AF XY: 0.0000406 AC XY: 3 AN XY: 73918

African (AFR) AF: 0.0000726 AC: 3 AN: 41344

American (AMR) AF: 0.00 AC: 0 AN: 15194

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3454

East Asian (EAS) AF: 0.00 AC: 0 AN: 5154

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4802

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10344

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 290

European-Non Finnish (NFE) AF: 0.0000295 AC: 2 AN: 67720

Other (OTH) AF: 0.00 AC: 0 AN: 2104

Alfa AF: 0.00 Hom.: 2091

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.27

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;