Variant 1-204149722-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_018208.4(ETNK2):c.499C>T(p.Arg167Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000598 in 1,594,152 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00053 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00061 ( 2 hom. )

Consequence

ETNK2
NM_018208.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.50

Variant links:

Genes affected

ETNK2 (HGNC:25575): (ethanolamine kinase 2) The protein encoded by this gene is a member of choline/ethanolamine kinase family which catalyzes the first step of phosphatidylethanolamine (PtdEtn) biosynthesis via the cytidine diphosphate (CDP) ethanolamine pathway. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]

ETNK2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.10966951).

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ETNK2	NM_018208.4 linkuse as main transcript	c.499C>T	p.Arg167Cys	missense_variant	2/8	ENST00000367202.9	NP_060678.2
ETNK2	NM_001297760.2 linkuse as main transcript	c.499C>T	p.Arg167Cys	missense_variant	2/8		NP_001284689.1
ETNK2	NM_001297762.2 linkuse as main transcript	c.499C>T	p.Arg167Cys	missense_variant	2/7		NP_001284691.1
ETNK2	NM_001297761.2 linkuse as main transcript	c.-17+1873C>T		intron_variant			NP_001284690.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ETNK2	ENST00000367202.9 linkuse as main transcript	c.499C>T	p.Arg167Cys	missense_variant	2/8	1	NM_018208.4	ENSP00000356170	P1	Q9NVF9-1
ETNK2	ENST00000367201.7 linkuse as main transcript	c.499C>T	p.Arg167Cys	missense_variant	2/8	2		ENSP00000356169		Q9NVF9-2
ETNK2	ENST00000444817.1 linkuse as main transcript	c.160C>T	p.Arg54Cys	missense_variant	1/4	5		ENSP00000406241

Frequencies

GnomAD3 genomes

AF:

0.000526

AC:

AN:

152226

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00109

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000273

AC:

AN:

219508

Hom.:

AF XY:

0.000253

AC XY:

AN XY:

118440

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000634

Gnomad ASJ exome

AF:

0.000107

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000374

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000567

Gnomad OTH exome

AF:

0.000181

GnomAD4 exome

AF:

0.000605

AC:

873

AN:

1441926

Hom.:

Cov.:

AF XY:

0.000554

AC XY:

396

AN XY:

715246

show subpopulations

Gnomad4 AFR exome

AF:

0.0000303

Gnomad4 AMR exome

AF:

0.0000474

Gnomad4 ASJ exome

AF:

0.0000389

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000604

Gnomad4 FIN exome

AF:

0.0000390

Gnomad4 NFE exome

AF:

0.000754

Gnomad4 OTH exome

AF:

0.000503

GnomAD4 genome

AF:

0.000526

AC:

AN:

152226

Hom.:

Cov.:

AF XY:

0.000484

AC XY:

AN XY:

74364

show subpopulations

Gnomad4 AFR

AF:

0.0000724

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00109

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000819

Hom.:

Bravo

AF:

0.000264

TwinsUK

AF:

0.00162

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.000231

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 02, 2023

The c.499C>T (p.R167C) alteration is located in exon 2 (coding exon 2) of the ETNK2 gene. This alteration results from a C to T substitution at nucleotide position 499, causing the arginine (R) at amino acid position 167 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.29

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.20

.;T;.

Eigen

Benign

0.013

Eigen_PC

Benign

0.061

FATHMM_MKL

Uncertain

0.81

LIST_S2

Uncertain

0.91

D;D;D

M_CAP

Benign

0.039

MetaRNN

Benign

0.11

T;T;T

MetaSVM

Benign

-0.75

MutationAssessor

Uncertain

2.0

M;M;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Benign

0.39

PROVEAN

Uncertain

-2.8

D;D;D

REVEL

Benign

0.18

Sift

Benign

0.16

T;T;T

Sift4G

Benign

0.095

T;T;.

Polyphen

1.0

D;B;.

Vest4

0.43

MVP

0.72

MPC

1.1

ClinPred

0.13

GERP RS

2.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.18

gMVP

0.71

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over