12-22661102-A-G

Variant names:

• chr12-22661102-A-G
• rs4963793
• NM_018638.5:c.597A>G

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_018638.5(ETNK1):​c.597A>G​(p.Glu199Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.139 in 1,611,224 control chromosomes in the GnomAD database, including 24,521 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.15 (2667 hom., cov: 32)
  • Exomes 𝑓: 0.14 (21854 hom.)
• Consequence: ETNK1 NM_018638.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0700
• Publications: 18 publications found

Genes affected

ETNK1 (HGNC:24649): (ethanolamine kinase 1) This gene encodes an ethanolamine kinase, which functions in the first committed step of the phosphatidylethanolamine synthesis pathway. This cytosolic enzyme is specific for ethanolamine and exhibits negligible kinase activity on choline. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.109).
• BP7: Synonymous conserved (PhyloP=0.07 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.668 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018638.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ETNK1	NM_018638.5	MANE Select	c.597A>G	p.Glu199Glu	synonymous	Exon 4 of 8	NP_061108.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ETNK1	ENST00000266517.9	TSL:1 MANE Select	c.597A>G	p.Glu199Glu	synonymous	Exon 4 of 8	ENSP00000266517.4
	ETNK1	ENST00000538218.2	TSL:1	c.597A>G	p.Glu199Glu	synonymous	Exon 4 of 9	ENSP00000446292.2
	ETNK1	ENST00000671733.1		c.864A>G	p.Glu288Glu	synonymous	Exon 4 of 8	ENSP00000500633.1

Frequencies

GnomAD3 genomes AF: 0.148 AC: 22537 AN: 152060 Hom.: 2669 Cov.: 32

Gnomad AFR AF: 0.0869

Gnomad AMI AF: 0.132

Gnomad AMR AF: 0.217

Gnomad ASJ AF: 0.127

Gnomad EAS AF: 0.687

Gnomad SAS AF: 0.222

Gnomad FIN AF: 0.214

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.114

Gnomad OTH AF: 0.169

GnomAD2 exomes AF: 0.198 AC: 49462 AN: 249638 AF XY: 0.192

Gnomad AFR exome AF: 0.0834

Gnomad AMR exome AF: 0.288

Gnomad ASJ exome AF: 0.131

Gnomad EAS exome AF: 0.700

Gnomad FIN exome AF: 0.213

Gnomad NFE exome AF: 0.112

Gnomad OTH exome AF: 0.184

GnomAD4 exome AF: 0.138 AC: 201053 AN: 1459046 Hom.: 21854 Cov.: 31 AF XY: 0.139 AC XY: 100925 AN XY: 725982

African (AFR) AF: 0.0860 AC: 2870 AN: 33372

American (AMR) AF: 0.275 AC: 12165 AN: 44210

Ashkenazi Jewish (ASJ) AF: 0.131 AC: 3417 AN: 26082

East Asian (EAS) AF: 0.685 AC: 27026 AN: 39446

South Asian (SAS) AF: 0.194 AC: 16633 AN: 85920

European-Finnish (FIN) AF: 0.210 AC: 11194 AN: 53388

Middle Eastern (MID) AF: 0.189 AC: 1090 AN: 5758

European-Non Finnish (NFE) AF: 0.105 AC: 116918 AN: 1110596

Other (OTH) AF: 0.162 AC: 9740 AN: 60274

GnomAD4 genome AF: 0.148 AC: 22530 AN: 152178 Hom.: 2667 Cov.: 32 AF XY: 0.158 AC XY: 11726 AN XY: 74390

African (AFR) AF: 0.0868 AC: 3605 AN: 41550

American (AMR) AF: 0.217 AC: 3311 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.127 AC: 442 AN: 3468

East Asian (EAS) AF: 0.687 AC: 3549 AN: 5166

South Asian (SAS) AF: 0.221 AC: 1065 AN: 4816

European-Finnish (FIN) AF: 0.214 AC: 2262 AN: 10586

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.114 AC: 7779 AN: 67992

Other (OTH) AF: 0.169 AC: 357 AN: 2112

Alfa AF: 0.125 Hom.: 2259

Bravo AF: 0.151

Asia WGS AF: 0.412 AC: 1433 AN: 3478

EpiCase AF: 0.120

EpiControl AF: 0.117

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	8.0
DANN	Benign	0.65
PhyloP100		0.070
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs4963793; hg19: chr12-22814036; COSMIC: COSV56886036;