12-22625455-C-T

Variant names:

• chr12-22625455-C-T
• rs567759665
• NM_018638.5:c.25C>T

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.25C>T​(p.Pro9Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000693 in 1,443,914 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P9A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: ETNK1 NM_018638.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.428
• Publications: 0 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: 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=0.11956456).

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.25C>T	p.Pro9Ser	missense	Exon 1 of 8	NP_061108.3
	ETNK1	NM_001039481.2		c.25C>T	p.Pro9Ser	missense	Exon 1 of 3	NP_001034570.2	Q86U68

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ETNK1	ENST00000266517.9	TSL:1 MANE Select	c.25C>T	p.Pro9Ser	missense	Exon 1 of 8	ENSP00000266517.4	A0A5K1VW28
	ETNK1	ENST00000538218.2	TSL:1	c.25C>T	p.Pro9Ser	missense	Exon 1 of 9	ENSP00000446292.2	H0YH69
	ETNK1	ENST00000335148.8	TSL:1	c.25C>T	p.Pro9Ser	missense	Exon 1 of 3	ENSP00000334041.4	Q86U68

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.93e-7 AC: 1 AN: 1443914 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 716844

African (AFR) AF: 0.00 AC: 0 AN: 33220

American (AMR) AF: 0.00 AC: 0 AN: 42984

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25622

East Asian (EAS) AF: 0.00 AC: 0 AN: 39152

South Asian (SAS) AF: 0.00 AC: 0 AN: 84110

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49490

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5746

European-Non Finnish (NFE) AF: 9.06e-7 AC: 1 AN: 1103874

Other (OTH) AF: 0.00 AC: 0 AN: 59716

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.094
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	16
DANN	Uncertain	0.98
DEOGEN2	Benign	0.014	T
Eigen	Benign	-0.36
Eigen_PC	Benign	-0.25
FATHMM_MKL	Benign	0.38	N
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.039	D
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N
PhyloP100		0.43
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.033
Sift	Benign	0.14	T
Sift4G	Benign	0.11	T
Polyphen		0.0	B
Vest4		0.14
MutPred		0.44		Gain of catalytic residue at P97 (P = 0.0071)
MVP		0.28
MPC		0.65
ClinPred		0.16	T
GERP RS		2.6
PromoterAI		0.28	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.046
gMVP		0.28
Mutation Taster		=88/12	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: rs567759665; hg19: chr12-22778389;