Genetic Variant NM_001010874.5:c.1026G>C (chr4-64280138-C-G) – ACMG Classification: Likely_benign (-1 pts)

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2BP4BP6_Moderate

The NM_001010874.5(TECRL):c.1026G>C(p.Lys342Asn) variant causes a missense 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. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 32)

Consequence

TECRL
NM_001010874.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.131

Publications

0 publications found

Variant links:

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

TECRL links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.30963567).

BP6

Variant 4-64280138-C-G is Benign according to our data. Variant chr4-64280138-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 3454637.Status of the report is criteria_provided_single_submitter, 1 stars.

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.1026G>C	p.Lys342Asn	missense	Exon 12 of 12	NP_001010874.2
	TECRL	NM_001363796.1		c.964+903G>C		intron	N/A	NP_001350725.1	E9PD39

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TECRL	ENST00000381210.8	TSL:1 MANE Select	c.1026G>C	p.Lys342Asn	missense	Exon 12 of 12	ENSP00000370607.3	Q5HYJ1
TECRL	ENST00000511997.1	TSL:1	c.*41G>C		3_prime_UTR	Exon 2 of 2	ENSP00000423975.1	H0Y9F0
TECRL	ENST00000941916.1		c.1251G>C	p.Lys417Asn	missense	Exon 13 of 13	ENSP00000611975.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Cardiovascular phenotype (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.26

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.58

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.56

Eigen

Benign

-0.31

Eigen_PC

Benign

-0.48

FATHMM_MKL

Benign

0.028

LIST_S2

Benign

0.55

M_CAP

Benign

0.012

MetaRNN

Benign

0.31

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.1

PhyloP100

-0.13

PrimateAI

Benign

0.44

PROVEAN

Benign

-2.3

REVEL

Benign

0.066

Sift

Benign

0.034

Sift4G

Benign

0.078

Polyphen

0.77

Vest4

0.28

MutPred

0.70

Loss of methylation at K342 (P = 0.0098)

MVP

0.21

MPC

0.044

ClinPred

0.88

GERP RS

-0.50

Varity_R

0.15

gMVP

0.65

Mutation Taster

=93/7

polymorphism

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over