1-204137188-G-C

Variant names:

• chr1-204137188-G-C
• rs61825753
• NM_018208.4:c.930C>G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_018208.4(ETNK2):​c.930C>G​(p.His310Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000555 in 1,613,968 control chromosomes in the GnomAD database, including 2 homozygotes. 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: 𝑓 0.00038 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00057 (2 hom.)
• Consequence: ETNK2 NM_018208.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0500
• 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: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.021765202).
• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

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.930C>G	p.His310Gln	missense	Exon 6 of 8	NP_060678.2	Q9NVF9-1
	ETNK2	NM_001297760.2		c.930C>G	p.His310Gln	missense	Exon 6 of 8	NP_001284689.1	Q9NVF9-2
	ETNK2	NM_001297762.2		c.807C>G	p.His269Gln	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.930C>G	p.His310Gln	missense	Exon 6 of 8	ENSP00000356170.4	Q9NVF9-1
	ETNK2	ENST00000367201.7	TSL:2	c.930C>G	p.His310Gln	missense	Exon 6 of 8	ENSP00000356169.3	Q9NVF9-2
	ETNK2	ENST00000422699.5	TSL:3	c.528C>G	p.His176Gln	missense	Exon 5 of 6	ENSP00000405497.1	Q5SXX8

Frequencies

GnomAD3 genomes AF: 0.000381 AC: 58 AN: 152212 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000830

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000691

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000590 AC: 148 AN: 251052 AF XY: 0.000641

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000955

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.000608

Gnomad OTH exome AF: 0.00131

GnomAD4 exome AF: 0.000573 AC: 838 AN: 1461638 Hom.: 2 Cov.: 31 AF XY: 0.000619 AC XY: 450 AN XY: 727114

African (AFR) AF: 0.0000597 AC: 2 AN: 33480

American (AMR) AF: 0.000895 AC: 40 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.0000765 AC: 2 AN: 26128

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39700

South Asian (SAS) AF: 0.00108 AC: 93 AN: 86254

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53400

Middle Eastern (MID) AF: 0.00139 AC: 8 AN: 5766

European-Non Finnish (NFE) AF: 0.000576 AC: 640 AN: 1111822

Other (OTH) AF: 0.000828 AC: 50 AN: 60372

GnomAD4 genome AF: 0.000381 AC: 58 AN: 152330 Hom.: 0 Cov.: 32 AF XY: 0.000349 AC XY: 26 AN XY: 74488

African (AFR) AF: 0.0000481 AC: 2 AN: 41568

American (AMR) AF: 0.000261 AC: 4 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.000831 AC: 4 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000691 AC: 47 AN: 68036

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.000405 Hom.: 0

Bravo AF: 0.000321

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.000610 AC: 74

EpiCase AF: 0.000709

EpiControl AF: 0.000652

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	0.086
BayesDel_addAF	Benign	-0.46	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	18
DANN	Benign	0.97
DEOGEN2	Benign	0.050	T
Eigen	Benign	-0.42
Eigen_PC	Benign	-0.36
FATHMM_MKL	Benign	0.077	N
LIST_S2	Benign	0.62	T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.022	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		-0.050
PrimateAI	Benign	0.20	T
PROVEAN	Benign	-0.93	N
REVEL	Benign	0.063
Sift	Benign	0.083	T
Sift4G	Benign	0.19	T
Polyphen		0.0040	B
Vest4		0.25
MutPred		0.47		Gain of helix (P = 0.062)
MVP		0.51
MPC		0.28
ClinPred		0.0095	T
GERP RS		1.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.060
gMVP		0.24
Mutation Taster		=98/2	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: rs61825753; hg19: chr1-204106316;