12-22661102-A-G

Position:

• chr12-22661102-A-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong 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

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

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ETNK1	NM_018638.5	c.597A>G	p.Glu199Glu	synonymous_variant	4/8	ENST00000266517.9	NP_061108.3
ETNK1	XM_017019580.2	c.597A>G	p.Glu199Glu	synonymous_variant	4/7		XP_016875069.2
ETNK1	XM_017019581.2	c.597A>G	p.Glu199Glu	synonymous_variant	4/5		XP_016875070.2
ETNK1	XM_047429100.1	c.597A>G	p.Glu199Glu	synonymous_variant	4/5		XP_047285056.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ETNK1	ENST00000266517.9	c.597A>G	p.Glu199Glu	synonymous_variant	4/8	1	NM_018638.5	ENSP00000266517.4

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

GnomAD3 exomes AF: 0.198 AC: 49462 AN: 249638 Hom.: 8083 AF XY: 0.192 AC XY: 25953 AN XY: 135046

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 SAS exome AF: 0.195

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

Gnomad4 AFR exome AF: 0.0860

Gnomad4 AMR exome AF: 0.275

Gnomad4 ASJ exome AF: 0.131

Gnomad4 EAS exome AF: 0.685

Gnomad4 SAS exome AF: 0.194

Gnomad4 FIN exome AF: 0.210

Gnomad4 NFE exome AF: 0.105

Gnomad4 OTH exome AF: 0.162

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

Gnomad4 AFR AF: 0.0868

Gnomad4 AMR AF: 0.217

Gnomad4 ASJ AF: 0.127

Gnomad4 EAS AF: 0.687

Gnomad4 SAS AF: 0.221

Gnomad4 FIN AF: 0.214

Gnomad4 NFE AF: 0.114

Gnomad4 OTH AF: 0.169

Alfa AF: 0.117 Hom.: 1099

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	8.0
DANN	Benign	0.65

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

Publications

LitVar

Other links and lift over

dbSNP: rs4963793; hg19: chr12-22814036; COSMIC: COSV56886036;