4-64280091-A-G

Variant names:

• chr4-64280091-A-G
• rs373062805
• NM_001010874.5:c.1073T>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001010874.5(TECRL):​c.1073T>C​(p.Met358Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M358K) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TECRL NM_001010874.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.48
• 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: Labcorp Genetics (formerly Invitae), G2P, Genomics England PanelApp, Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.1073T>C	p.Met358Thr	missense	Exon 12 of 12	NP_001010874.2
	TECRL	NM_001363796.1		c.964+950T>C		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.1073T>C	p.Met358Thr	missense	Exon 12 of 12	ENSP00000370607.3	Q5HYJ1
	TECRL	ENST00000511997.1	TSL:1	c.*88T>C		3_prime_UTR	Exon 2 of 2	ENSP00000423975.1	H0Y9F0
	TECRL	ENST00000941916.1		c.1298T>C	p.Met433Thr	missense	Exon 13 of 13	ENSP00000611975.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.55
BayesDel_addAF	Uncertain	0.054	T
BayesDel_noAF	Benign	-0.16
CADD	Benign	23
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.59	D
Eigen	Benign	0.11
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.64	T
M_CAP	Benign	0.017	T
MetaRNN	Uncertain	0.64	D
MetaSVM	Benign	-0.94	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		5.5
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.23
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0020	D
Polyphen		0.033	B
Vest4		0.57
MutPred		0.84		Loss of stability (P = 0.0453)
MVP		0.38
MPC		0.017
ClinPred		0.84	D
GERP RS		5.1
Varity_R		0.60
gMVP		0.60
Mutation Taster		=89/11	polymorphism

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: rs373062805; hg19: chr4-65145809; COSMIC: COSV67088598;