12-22625251-C-G

Variant names:

• chr12-22625251-C-G
• rs150714252
• NM_018638.5:c.-180C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_018638.5(ETNK1):​c.-180C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,459,422 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ETNK1 NM_018638.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.825
• Publications: 1 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]

ETNK1-DT (HGNC:55486): (ETNK1 divergent transcript)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.085501015).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ETNK1	NM_018638.5	MANE Select	c.-180C>G		5_prime_UTR	Exon 1 of 8	NP_061108.3
	ETNK1	NM_001039481.2		c.-180C>G		5_prime_UTR	Exon 1 of 3	NP_001034570.2	Q86U68
	ETNK1-DT	NR_135030.1		n.-205G>C		upstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ETNK1	ENST00000266517.9	TSL:1 MANE Select	c.-180C>G		5_prime_UTR	Exon 1 of 8	ENSP00000266517.4	A0A5K1VW28
	ETNK1	ENST00000538218.2	TSL:1	c.-180C>G		5_prime_UTR	Exon 1 of 9	ENSP00000446292.2	H0YH69
	ETNK1	ENST00000335148.8	TSL:1	c.-180C>G		5_prime_UTR	Exon 1 of 3	ENSP00000334041.4	Q86U68

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1459422 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 725978

African (AFR) AF: 0.0000299 AC: 1 AN: 33444

American (AMR) AF: 0.00 AC: 0 AN: 44638

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26068

East Asian (EAS) AF: 0.00 AC: 0 AN: 39654

South Asian (SAS) AF: 0.00 AC: 0 AN: 86170

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51924

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111504

Other (OTH) AF: 0.00 AC: 0 AN: 60260

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	7.4
DANN	Benign	0.95
DEOGEN2	Benign	0.0048	T
Eigen	Benign	-0.95
Eigen_PC	Benign	-0.92
FATHMM_MKL	Benign	0.055	N
LIST_S2	Benign	0.53	T
M_CAP	Benign	0.047	D
MetaRNN	Benign	0.086	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		-0.82
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-0.40	N
REVEL	Benign	0.079
Sift	Benign	0.089	T
Sift4G	Uncertain	0.027	D
Polyphen		0.0	B
Vest4		0.20
MutPred		0.31		Gain of catalytic residue at S34 (P = 0.0044)
MVP		0.51
MPC		0.83
ClinPred		0.087	T
GERP RS		1.8
PromoterAI		-0.051	Neutral
Varity_R		0.12
gMVP		0.22
Mutation Taster		=99/1	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: rs150714252; hg19: chr12-22778185;