1-204151735-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_018208.4(ETNK2):ā€‹c.118C>Gā€‹(p.Arg40Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000189 in 1,533,886 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 Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000013 ( 0 hom., cov: 32)
Exomes š‘“: 0.000020 ( 0 hom. )

Consequence

ETNK2
NM_018208.4 missense

Scores

1
1
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.94
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.118935764).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ETNK2NM_018208.4 linkuse as main transcriptc.118C>G p.Arg40Gly missense_variant 1/8 ENST00000367202.9 NP_060678.2
ETNK2NM_001297760.2 linkuse as main transcriptc.118C>G p.Arg40Gly missense_variant 1/8 NP_001284689.1
ETNK2NM_001297762.2 linkuse as main transcriptc.118C>G p.Arg40Gly missense_variant 1/7 NP_001284691.1
ETNK2NM_001297761.2 linkuse as main transcriptc.-157C>G 5_prime_UTR_variant 1/7 NP_001284690.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ETNK2ENST00000367202.9 linkuse as main transcriptc.118C>G p.Arg40Gly missense_variant 1/81 NM_018208.4 ENSP00000356170 P1Q9NVF9-1
ETNK2ENST00000367201.7 linkuse as main transcriptc.118C>G p.Arg40Gly missense_variant 1/82 ENSP00000356169 Q9NVF9-2

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152110
Hom.:
0
Cov.:
32
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:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000237
AC:
3
AN:
126564
Hom.:
0
AF XY:
0.0000145
AC XY:
1
AN XY:
69042
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000659
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000195
AC:
27
AN:
1381776
Hom.:
0
Cov.:
30
AF XY:
0.0000235
AC XY:
16
AN XY:
681244
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000252
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152110
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74304
show subpopulations
Gnomad4 AFR
AF:
0.00
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:
0.0000294
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000794
Hom.:
0
Bravo
AF:
0.0000189

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 submitterclinical testingAmbry GeneticsJul 26, 2022The c.118C>G (p.R40G) alteration is located in exon 1 (coding exon 1) of the ETNK2 gene. This alteration results from a C to G substitution at nucleotide position 118, causing the arginine (R) at amino acid position 40 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
0.067
BayesDel_addAF
Benign
-0.34
T
BayesDel_noAF
Benign
-0.54
CADD
Benign
19
DANN
Benign
0.97
DEOGEN2
Benign
0.038
.;T
Eigen
Benign
-0.60
Eigen_PC
Benign
-0.52
FATHMM_MKL
Benign
0.52
D
LIST_S2
Benign
0.78
T;T
M_CAP
Pathogenic
0.51
D
MetaRNN
Benign
0.12
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.69
N;N
MutationTaster
Benign
1.0
N;N;N
PrimateAI
Uncertain
0.73
T
PROVEAN
Benign
-0.88
N;N
REVEL
Benign
0.065
Sift
Benign
0.051
T;T
Sift4G
Benign
0.17
T;T
Polyphen
0.73
P;B
Vest4
0.066
MutPred
0.20
Gain of glycosylation at S36 (P = 0.0898);Gain of glycosylation at S36 (P = 0.0898);
MVP
0.56
MPC
0.38
ClinPred
0.086
T
GERP RS
-0.43
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.6
Varity_R
0.069
gMVP
0.32

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.

Other links and lift over

dbSNP: rs1296606725; hg19: chr1-204120863; API