Variant 1-204151819-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_018208.4(ETNK2):c.34G>T(p.Ala12Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000358 in 1,479,410 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000038 ( 0 hom. )

Consequence

ETNK2
NM_018208.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.187

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 -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.05960524).

BP6

Variant 1-204151819-C-A is Benign according to our data. Variant chr1-204151819-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 3090709.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
ETNK2	NM_018208.4 linkuse as main transcript	c.34G>T	p.Ala12Ser	missense_variant	1/8	ENST00000367202.9
ETNK2	NM_001297760.2 linkuse as main transcript	c.34G>T	p.Ala12Ser	missense_variant	1/8
ETNK2	NM_001297762.2 linkuse as main transcript	c.34G>T	p.Ala12Ser	missense_variant	1/7
ETNK2	NM_001297761.2 linkuse as main transcript	c.-241G>T		5_prime_UTR_variant	1/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ETNK2	ENST00000367202.9 linkuse as main transcript	c.34G>T	p.Ala12Ser	missense_variant	1/8	1	NM_018208.4	P1	Q9NVF9-1
ETNK2	ENST00000367201.7 linkuse as main transcript	c.34G>T	p.Ala12Ser	missense_variant	1/8	2			Q9NVF9-2

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152116

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000387

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000136

AC:

AN:

73572

Hom.:

AF XY:

0.0000257

AC XY:

AN XY:

38874

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000149

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000384

AC:

AN:

1327294

Hom.:

Cov.:

AF XY:

0.0000385

AC XY:

AN XY:

649708

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00151

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152116

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74310

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000387

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 06, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.61

CADD

Benign

8.0

DANN

Benign

0.94

DEOGEN2

Benign

0.016

.;T

Eigen

Benign

-0.86

Eigen_PC

Benign

-0.69

FATHMM_MKL

Benign

0.037

LIST_S2

Benign

0.57

T;T

M_CAP

Pathogenic

0.45

MetaRNN

Benign

0.060

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.90

N;N

MutationTaster

Benign

1.0

D;N;N

PrimateAI

Uncertain

0.77

PROVEAN

Benign

-0.12

N;N

REVEL

Benign

0.071

Sift

Benign

0.46

T;T

Sift4G

Benign

0.69

T;T

Polyphen

0.013

B;B

Vest4

0.067

MutPred

0.10

Gain of glycosylation at A12 (P = 0.019);Gain of glycosylation at A12 (P = 0.019);

MVP

0.33

MPC

0.26

ClinPred

0.075

GERP RS

1.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.047

gMVP

0.16

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