rs144439568

Variant names:

• chr1-204137163-T-A
• rs144439568
• NM_018208.4:c.955A>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_018208.4(ETNK2):​c.955A>T​(p.Met319Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ETNK2 NM_018208.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.462
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0976139).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018208.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ETNK2	NM_018208.4	MANE Select	c.955A>T	p.Met319Leu	missense	Exon 6 of 8	NP_060678.2	Q9NVF9-1
	ETNK2	NM_001297760.2		c.955A>T	p.Met319Leu	missense	Exon 6 of 8	NP_001284689.1	Q9NVF9-2
	ETNK2	NM_001297762.2		c.832A>T	p.Met278Leu	missense	Exon 5 of 7	NP_001284691.1	Q9NVF9-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ETNK2	ENST00000367202.9	TSL:1 MANE Select	c.955A>T	p.Met319Leu	missense	Exon 6 of 8	ENSP00000356170.4	Q9NVF9-1
	ETNK2	ENST00000367201.7	TSL:2	c.955A>T	p.Met319Leu	missense	Exon 6 of 8	ENSP00000356169.3	Q9NVF9-2
	ETNK2	ENST00000422699.5	TSL:3	c.553A>T	p.Met185Leu	missense	Exon 5 of 6	ENSP00000405497.1	Q5SXX8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00 AC: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	0.0080
DANN	Benign	0.78
DEOGEN2	Benign	0.013	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.080	N
LIST_S2	Benign	0.57	T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.038	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		-0.46
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-0.44	N
REVEL	Benign	0.042
Sift	Benign	0.71	T
Sift4G	Benign	0.59	T
Polyphen		0.010	B
Vest4		0.29
MutPred		0.42		Gain of loop (P = 0.0045)
MVP		0.16
MPC		0.26
ClinPred		0.014	T
GERP RS		-5.0
Varity_R		0.072
gMVP		0.16
Mutation Taster		=105/95	polymorphism

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

Other links and lift over

dbSNP: rs144439568; hg19: chr1-204106291;