Variant chr1-204137188-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The ENST00000367202.9(ETNK2):c.930C>G(p.His310Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000555 in 1,613,968 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00038 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00057 ( 2 hom. )

Consequence

ETNK2
ENST00000367202.9 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0500

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 Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.021765202).

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ETNK2	NM_018208.4 linkuse as main transcript	c.930C>G	p.His310Gln	missense_variant	6/8	ENST00000367202.9	NP_060678.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ETNK2	ENST00000367202.9 linkuse as main transcript	c.930C>G	p.His310Gln	missense_variant	6/8	1	NM_018208.4	ENSP00000356170	P1	Q9NVF9-1

Frequencies

GnomAD3 genomes

AF:

0.000381

AC:

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000830

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000691

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000590

AC:

148

AN:

251052

Hom.:

AF XY:

0.000641

AC XY:

AN XY:

135686

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000955

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00118

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.000608

Gnomad OTH exome

AF:

0.00131

GnomAD4 exome

AF:

0.000573

AC:

838

AN:

1461638

Hom.:

Cov.:

AF XY:

0.000619

AC XY:

450

AN XY:

727114

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

Gnomad4 AMR exome

AF:

0.000895

Gnomad4 ASJ exome

AF:

0.0000765

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00108

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000576

Gnomad4 OTH exome

AF:

0.000828

GnomAD4 genome

AF:

0.000381

AC:

AN:

152330

Hom.:

Cov.:

AF XY:

0.000349

AC XY:

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.000261

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000831

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000691

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000405

Hom.:

Bravo

AF:

0.000321

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000610

AC:

EpiCase

AF:

0.000709

EpiControl

AF:

0.000652

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

Dec 27, 2023

The c.930C>G (p.H310Q) alteration is located in exon 6 (coding exon 6) of the ETNK2 gene. This alteration results from a C to G substitution at nucleotide position 930, causing the histidine (H) at amino acid position 310 to be replaced by a glutamine (Q). 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

0.086

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.050

.;T;T;T

Eigen

Benign

-0.42

Eigen_PC

Benign

-0.36

FATHMM_MKL

Benign

0.077

LIST_S2

Benign

0.62

T;T;T;T

M_CAP

Benign

0.016

MetaRNN

Benign

0.022

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

N;N;.;.

MutationTaster

Benign

1.0

N;N;N;N;N

PrimateAI

Benign

0.20

PROVEAN

Benign

-0.93

N;N;N;N

REVEL

Benign

0.063

Sift

Benign

0.083

T;T;T;T

Sift4G

Benign

0.19

T;T;.;.

Polyphen

0.0040

B;B;.;.

Vest4

0.25

MutPred

0.47

Gain of helix (P = 0.062);Gain of helix (P = 0.062);.;.;

MVP

0.51

MPC

0.28

ClinPred

0.0095

GERP RS

1.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.060

gMVP

0.24

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