Variant 1-204151717-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_018208.4(ETNK2):c.136C>T(p.Pro46Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000167 in 1,542,610 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.00012 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00017 ( 0 hom. )

Consequence

ETNK2
NM_018208.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.65

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 -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.029232591).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ETNK2	NM_018208.4 linkuse as main transcript	c.136C>T	p.Pro46Ser	missense_variant	1/8	ENST00000367202.9	NP_060678.2
ETNK2	NM_001297760.2 linkuse as main transcript	c.136C>T	p.Pro46Ser	missense_variant	1/8		NP_001284689.1
ETNK2	NM_001297762.2 linkuse as main transcript	c.136C>T	p.Pro46Ser	missense_variant	1/7		NP_001284691.1
ETNK2	NM_001297761.2 linkuse as main transcript	c.-139C>T		5_prime_UTR_variant	1/7		NP_001284690.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ETNK2	ENST00000367202.9 linkuse as main transcript	c.136C>T	p.Pro46Ser	missense_variant	1/8	1	NM_018208.4	ENSP00000356170	P1	Q9NVF9-1
ETNK2	ENST00000367201.7 linkuse as main transcript	c.136C>T	p.Pro46Ser	missense_variant	1/8	2		ENSP00000356169		Q9NVF9-2

Frequencies

GnomAD3 genomes

AF:

0.000125

AC:

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.000865

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000221

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000220

AC:

AN:

136328

Hom.:

AF XY:

0.000216

AC XY:

AN XY:

74086

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00230

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000911

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000184

Gnomad OTH exome

AF:

0.000253

GnomAD4 exome

AF:

0.000171

AC:

238

AN:

1390408

Hom.:

Cov.:

AF XY:

0.000159

AC XY:

109

AN XY:

685572

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00282

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000102

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000127

Gnomad4 OTH exome

AF:

0.000347

GnomAD4 genome

AF:

0.000125

AC:

AN:

152202

Hom.:

Cov.:

AF XY:

0.0000941

AC XY:

AN XY:

74354

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.000865

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000221

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000327

Hom.:

Bravo

AF:

0.000136

ExAC

AF:

0.000192

AC:

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

Aug 01, 2022

The c.136C>T (p.P46S) alteration is located in exon 1 (coding exon 1) of the ETNK2 gene. This alteration results from a C to T substitution at nucleotide position 136, causing the proline (P) at amino acid position 46 to be replaced by a serine (S). 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

0.078

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.025

.;T

Eigen

Benign

-0.17

Eigen_PC

Benign

-0.086

FATHMM_MKL

Benign

0.70

LIST_S2

Benign

0.73

T;T

M_CAP

Pathogenic

0.61

MetaRNN

Benign

0.029

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.5

L;L

MutationTaster

Benign

0.62

N;N;N

PrimateAI

Uncertain

0.76

PROVEAN

Benign

-1.5

N;N

REVEL

Benign

0.048

Sift

Benign

0.079

T;D

Sift4G

Benign

0.36

T;T

Polyphen

0.56

P;B

Vest4

0.12

MVP

0.58

MPC

0.38

ClinPred

0.066

GERP RS

3.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.076

gMVP

0.40

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

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