NM_018208.4:c.271G>A

Variant names:

• chr1-204149950-C-T
• NM_018208.4:c.271G>A

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_018208.4(ETNK2):​c.271G>A​(p.Gly91Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000855 in 1,169,828 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 8.5e-7 (0 hom.)
• Consequence: ETNK2 NM_018208.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.24
• 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: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.945

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.271G>A	p.Gly91Ser	missense	Exon 2 of 8	NP_060678.2	Q9NVF9-1
	ETNK2	NM_001297760.2		c.271G>A	p.Gly91Ser	missense	Exon 2 of 8	NP_001284689.1	Q9NVF9-2
	ETNK2	NM_001297762.2		c.271G>A	p.Gly91Ser	missense	Exon 2 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.271G>A	p.Gly91Ser	missense	Exon 2 of 8	ENSP00000356170.4	Q9NVF9-1
	ETNK2	ENST00000367201.7	TSL:2	c.271G>A	p.Gly91Ser	missense	Exon 2 of 8	ENSP00000356169.3	Q9NVF9-2
	ETNK2	ENST00000429525.1	TSL:4	c.-42G>A		5_prime_UTR	Exon 3 of 3	ENSP00000394618.1	B7ZC35

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 8.55e-7 AC: 1 AN: 1169828 Hom.: 0 Cov.: 36 AF XY: 0.00000174 AC XY: 1 AN XY: 573900

African (AFR) AF: 0.00 AC: 0 AN: 24910

American (AMR) AF: 0.00 AC: 0 AN: 28744

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16494

East Asian (EAS) AF: 0.00 AC: 0 AN: 15030

South Asian (SAS) AF: 0.00 AC: 0 AN: 77082

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 29330

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4350

European-Non Finnish (NFE) AF: 0.00000107 AC: 1 AN: 931240

Other (OTH) AF: 0.00 AC: 0 AN: 42648

GnomAD4 genome Cov.: 31

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	Pathogenic	0.93
BayesDel_addAF	Pathogenic	0.43	D
BayesDel_noAF	Pathogenic	0.38
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.56	D
Eigen	Pathogenic	0.87
Eigen_PC	Pathogenic	0.83
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Uncertain	0.11	D
MetaRNN	Pathogenic	0.94	D
MetaSVM	Uncertain	0.78	D
MutationAssessor	Uncertain	2.4	M
PhyloP100		7.2
PrimateAI	Pathogenic	0.89	D
PROVEAN	Pathogenic	-5.6	D
REVEL	Pathogenic	0.92
Sift	Uncertain	0.0020	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.93
MutPred		0.79		Gain of MoRF binding (P = 0.0921)
MVP		0.97
MPC		0.94
ClinPred		1.0	D
GERP RS		5.5
PromoterAI		-0.036	Neutral
Varity_R		0.68
gMVP		0.88
Mutation Taster		=54/46	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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

hg19: chr1-204119078;