12-22625222-C-T

Variant summary

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

The NM_018638.5(ETNK1):​c.-209C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,458,832 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: not found (cov: 33)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

ETNK1
NM_018638.5 5_prime_UTR

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.838
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-DT (HGNC:55486): (ETNK1 divergent transcript)

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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=0.106725246).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ETNK1NM_018638.5 linkc.-209C>T 5_prime_UTR_variant Exon 1 of 8 ENST00000266517.9 NP_061108.3 Q9HBU6

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ETNK1ENST00000266517 linkc.-209C>T 5_prime_UTR_variant Exon 1 of 8 1 NM_018638.5 ENSP00000266517.4 A0A5K1VW28

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.00000838
AC:
2
AN:
238664
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
131104
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:
0.0000330
Gnomad FIN exome
AF:
0.0000475
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000206
AC:
3
AN:
1458832
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
725518
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:
0.0000116
Gnomad4 FIN exome
AF:
0.0000192
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
ExAC
AF:
0.00000827
AC:
1

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jan 27, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.59C>T (p.A20V) 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 59, causing the alanine (A) at amino acid position 20 to be replaced by a valine (V). 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
0.10
BayesDel_addAF
Benign
-0.17
T
BayesDel_noAF
Benign
-0.48
CADD
Benign
9.2
DANN
Benign
0.91
DEOGEN2
Benign
0.0063
T;.
Eigen
Benign
-0.74
Eigen_PC
Benign
-0.82
FATHMM_MKL
Benign
0.082
N
LIST_S2
Benign
0.47
T;T
M_CAP
Benign
0.028
D
MetaRNN
Benign
0.11
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.0
N;N
PrimateAI
Uncertain
0.58
T
PROVEAN
Benign
-0.14
N;N
REVEL
Benign
0.042
Sift
Uncertain
0.0090
D;D
Sift4G
Benign
0.18
T;T
Polyphen
0.0020
B;.
Vest4
0.23
MVP
0.50
MPC
0.64
ClinPred
0.086
T
GERP RS
1.6
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.049
gMVP
0.17

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: rs756513365; hg19: chr12-22778156; API