rs374969247

Variant names:

• chr1-204140113-C-A
• rs374969247
• NM_018208.4:c.790G>T

Your query was ambiguous. Multiple possible variants found:

• chr1-204140113-C-A
• chr1-204140113-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_018208.4(ETNK2):​c.790G>T​(p.Val264Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,248 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V264M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: ETNK2 NM_018208.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.22

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ETNK2	NM_018208.4	c.790G>T	p.Val264Leu	missense_variant	Exon 5 of 8	ENST00000367202.9	NP_060678.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ETNK2	ENST00000367202.9	c.790G>T	p.Val264Leu	missense_variant	Exon 5 of 8	1	NM_018208.4	ENSP00000356170.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251066 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135692

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: 0.00000882

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461248 Hom.: 0 Cov.: 30 AF XY: 0.00000413 AC XY: 3 AN XY: 726962

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: 0.00000450

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.68
BayesDel_addAF	Uncertain	0.077	D
BayesDel_noAF	Benign	-0.13
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.22	.;T;T;T;.
Eigen	Uncertain	0.32
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.94	D;D;D;D;D
M_CAP	Benign	0.047	D
MetaRNN	Uncertain	0.67	D;D;D;D;D
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.99	L;L;.;.;.
PrimateAI	Uncertain	0.65	T
PROVEAN	Uncertain	-2.8	D;D;D;D;D
REVEL	Benign	0.26
Sift	Uncertain	0.0020	D;D;D;D;D
Sift4G	Uncertain	0.049	D;T;.;.;.
Polyphen		1.0	D;D;.;.;.
Vest4		0.73
MutPred		0.56		Gain of catalytic residue at V264 (P = 0.0086);Gain of catalytic residue at V264 (P = 0.0086);.;.;.;
MVP		0.37
MPC		0.82
ClinPred		0.92	D
GERP RS		5.4
Varity_R		0.53
gMVP		0.70

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

Other links and lift over

dbSNP: rs374969247; hg19: chr1-204109241;