chr1-204149896-C-T

Variant names:

• chr1-204149896-C-T
• rs746164408
• NM_018208.4:c.325G>A

Variant summary

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

The NM_018208.4(ETNK2):​c.325G>A​(p.Val109Met) variant causes a missense change. The variant allele was found at a frequency of 0.000019 in 1,579,046 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000020 (0 hom.)
• Consequence: ETNK2 NM_018208.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.51
• 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 2 ACMG points.

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

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.325G>A	p.Val109Met	missense	Exon 2 of 8	NP_060678.2	Q9NVF9-1
	ETNK2	NM_001297760.2		c.325G>A	p.Val109Met	missense	Exon 2 of 8	NP_001284689.1	Q9NVF9-2
	ETNK2	NM_001297762.2		c.325G>A	p.Val109Met	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.325G>A	p.Val109Met	missense	Exon 2 of 8	ENSP00000356170.4	Q9NVF9-1
	ETNK2	ENST00000367201.7	TSL:2	c.325G>A	p.Val109Met	missense	Exon 2 of 8	ENSP00000356169.3	Q9NVF9-2
	ETNK2	ENST00000429525.1	TSL:4	c.13G>A	p.Val5Met	missense	Exon 3 of 3	ENSP00000394618.1	B7ZC35

Frequencies

GnomAD3 genomes AF: 0.00000659 AC: 1 AN: 151840 Hom.: 0 Cov.: 32

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000309 AC: 6 AN: 194356 AF XY: 0.0000192

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000106

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000554

Gnomad NFE exome AF: 0.0000120

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000203 AC: 29 AN: 1427206 Hom.: 0 Cov.: 35 AF XY: 0.0000113 AC XY: 8 AN XY: 706670

African (AFR) AF: 0.0000307 AC: 1 AN: 32548

American (AMR) AF: 0.0000757 AC: 3 AN: 39606

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25514

East Asian (EAS) AF: 0.0000267 AC: 1 AN: 37508

South Asian (SAS) AF: 0.0000123 AC: 1 AN: 81342

European-Finnish (FIN) AF: 0.0000392 AC: 2 AN: 51028

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5736

European-Non Finnish (NFE) AF: 0.0000174 AC: 19 AN: 1094788

Other (OTH) AF: 0.0000338 AC: 2 AN: 59136

GnomAD4 genome AF: 0.00000659 AC: 1 AN: 151840 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74142

African (AFR) AF: 0.00 AC: 0 AN: 41332

American (AMR) AF: 0.00 AC: 0 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5156

South Asian (SAS) AF: 0.00 AC: 0 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10546

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 312

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67962

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000283 Hom.: 0

Bravo AF: 0.0000227

ExAC AF: 0.0000166 AC: 2

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	Uncertain	0.51
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.19
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.27	T
Eigen	Uncertain	0.59
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Benign	0.71	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.028	D
MetaRNN	Uncertain	0.67	D
MetaSVM	Uncertain	0.10	D
MutationAssessor	Pathogenic	3.0	M
PhyloP100		4.5
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-2.4	N
REVEL	Uncertain	0.45
Sift	Uncertain	0.021	D
Sift4G	Uncertain	0.0020	D
Polyphen		0.62	P
Vest4		0.40
MutPred		0.74		Loss of sheet (P = 0.1398)
MVP		0.57
MPC		0.52
ClinPred		0.72	D
GERP RS		4.6
PromoterAI		-0.011	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.49
gMVP		0.79
Mutation Taster		=55/45	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: rs746164408; hg19: chr1-204119024;