Variant chr12-22625251-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_018638.5(ETNK1):c.-180C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000261 in 1,611,758 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 0.00032 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00025 ( 0 hom. )

Consequence

ETNK1
NM_018638.5 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.825

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 Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.017269164).

BS2

High AC in GnomAd4 at 49 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ETNK1	NM_018638.5 linkuse as main transcript	c.-180C>T		5_prime_UTR_premature_start_codon_gain_variant	1/8	ENST00000266517.9	NP_061108.3	Q9HBU6
ETNK1	NM_018638.5 linkuse as main transcript	c.-180C>T		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.-180C>T		5_prime_UTR_premature_start_codon_gain_variant	1/8	1	NM_018638.5	ENSP00000266517.4		A0A5K1VW28
ETNK1	ENST00000266517.9 linkuse as main transcript	c.-180C>T		5_prime_UTR_variant	1/8	1	NM_018638.5	ENSP00000266517.4		A0A5K1VW28

Frequencies

GnomAD3 genomes

AF:

0.000322

AC:

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00111

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:

0.000367

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.000265

AC:

AN:

237408

Hom.:

AF XY:

0.000215

AC XY:

AN XY:

130428

show subpopulations

Gnomad AFR exome

AF:

0.0000705

Gnomad AMR exome

AF:

0.000675

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000961

Gnomad NFE exome

AF:

0.000334

Gnomad OTH exome

AF:

0.000346

GnomAD4 exome

AF:

0.000255

AC:

372

AN:

1459420

Hom.:

Cov.:

AF XY:

0.000237

AC XY:

172

AN XY:

725978

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000919

Gnomad4 ASJ exome

AF:

0.0000384

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000385

Gnomad4 NFE exome

AF:

0.000277

Gnomad4 OTH exome

AF:

0.000299

GnomAD4 genome

AF:

0.000322

AC:

AN:

152338

Hom.:

Cov.:

AF XY:

0.000295

AC XY:

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.0000721

Gnomad4 AMR

AF:

0.00111

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000367

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.000211

Hom.:

Bravo

AF:

0.000295

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000265

AC:

EpiCase

AF:

0.000273

EpiControl

AF:

0.000238

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

Sep 17, 2021

The c.88C>T (p.R30W) alteration is located in exon 1 (coding exon 1) of the ETNK1 gene. This alteration results from a C to T substitution at nucleotide position 88, causing the arginine (R) at amino acid position 30 to be replaced by a tryptophan (W). 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

0.18

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0047

T;.

Eigen

Benign

-0.95

Eigen_PC

Benign

-0.92

FATHMM_MKL

Benign

0.064

LIST_S2

Benign

0.66

T;T

M_CAP

Benign

0.052

MetaRNN

Benign

0.017

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

N;N

PrimateAI

Uncertain

0.66

PROVEAN

Benign

-0.45

N;N

REVEL

Benign

0.080

Sift

Benign

0.079

T;T

Sift4G

Uncertain

0.0060

D;D

Polyphen

0.0

B;.

Vest4

0.28

MVP

0.46

MPC

0.67

ClinPred

0.053

GERP RS

1.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.073

gMVP

0.19

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