Variant 12-22625188-A-G 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_018638.5(ETNK1):c.-243A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000336 in 1,607,456 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000098 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000027 ( 0 hom. )

Consequence

ETNK1
NM_018638.5 5_prime_UTR

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.35

Variant links:

Genes affected

ETNK1 (HGNC:24649): (ethanolamine kinase 1) This gene encodes an ethanolamine kinase, which functions in the first committed step of the phosphatidylethanolamine synthesis pathway. This cytosolic enzyme is specific for ethanolamine and exhibits negligible kinase activity on choline. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Jul 2008]

ETNK1 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=0.079576075).

BS2

High AC in GnomAd4 at 15 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ETNK1	NM_018638.5 linkuse as main transcript	c.-243A>G		5_prime_UTR_variant	1/8	ENST00000266517.9	NP_061108.3	Q9HBU6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ETNK1	ENST00000266517.9 linkuse as main transcript	c.-243A>G		5_prime_UTR_variant	1/8	1	NM_018638.5	ENSP00000266517.4		A0A5K1VW28

Frequencies

GnomAD3 genomes

AF:

0.0000985

AC:

AN:

152224

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000265

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000441

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000427

AC:

AN:

234124

Hom.:

AF XY:

0.0000387

AC XY:

AN XY:

129248

show subpopulations

Gnomad AFR exome

AF:

0.000361

Gnomad AMR exome

AF:

0.0000294

Gnomad ASJ exome

AF:

0.000106

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000333

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000194

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000268

AC:

AN:

1455114

Hom.:

Cov.:

AF XY:

0.0000263

AC XY:

AN XY:

723110

show subpopulations

Gnomad4 AFR exome

AF:

0.000330

Gnomad4 AMR exome

AF:

0.0000901

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000505

Gnomad4 SAS exome

AF:

0.0000233

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000171

Gnomad4 OTH exome

AF:

0.0000167

GnomAD4 genome

AF:

0.0000985

AC:

AN:

152342

Hom.:

Cov.:

AF XY:

0.0000671

AC XY:

AN XY:

74506

show subpopulations

Gnomad4 AFR

AF:

0.000265

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000169

Hom.:

Bravo

AF:

0.000125

ExAC

AF:

0.0000166

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

Jun 01, 2023

The c.25A>G (p.S9G) alteration is located in exon 1 (coding exon 1) of the ETNK1 gene. This alteration results from a A to G substitution at nucleotide position 25, causing the serine (S) at amino acid position 9 to be replaced by a glycine (G). 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

0.066

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.0048

T;.

Eigen

Benign

-0.57

Eigen_PC

Benign

-0.48

FATHMM_MKL

Benign

0.57

LIST_S2

Benign

0.38

T;T

M_CAP

Benign

0.036

MetaRNN

Benign

0.080

T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.0

N;N

PrimateAI

Uncertain

0.59

PROVEAN

Benign

-0.16

N;N

REVEL

Benign

0.13

Sift

Uncertain

0.015

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

0.0020

B;.

Vest4

0.37

MVP

0.57

MPC

0.73

ClinPred

0.092

GERP RS

4.6

Varity_R

0.14

gMVP

0.14

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