chr1-204132194-A-T

Position:

• chr1-204132194-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_018208.4(ETNK2):​c.1151T>A​(p.Met384Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000141 in 1,420,074 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ETNK2 NM_018208.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.94

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ETNK2	NM_018208.4	c.1151T>A	p.Met384Lys	missense_variant	8/8	ENST00000367202.9	NP_060678.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ETNK2	ENST00000367202.9	c.1151T>A	p.Met384Lys	missense_variant	8/8	1	NM_018208.4	ENSP00000356170	P1
ETNK2	ENST00000422072.5	c.440T>A	p.Met147Lys	missense_variant	5/5	3		ENSP00000410580
ETNK2	ENST00000367197.5	c.197T>A	p.Met66Lys	missense_variant	5/5	3		ENSP00000356165
ETNK2	ENST00000367201.7	c.*72T>A		3_prime_UTR_variant	8/8	2		ENSP00000356169

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000141 AC: 2 AN: 1420074 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 702124

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000183

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.0000113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 30, 2022

The c.1151T>A (p.M384K) alteration is located in exon 8 (coding exon 8) of the ETNK2 gene. This alteration results from a T to A substitution at nucleotide position 1151, causing the methionine (M) at amino acid position 384 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.35
BayesDel_addAF	Uncertain	0.033	T
BayesDel_noAF	Benign	-0.19
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.11	T;T
Eigen	Uncertain	0.40
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.70	T;T
M_CAP	Benign	0.045	D
MetaRNN	Uncertain	0.63	D;D
MetaSVM	Benign	-0.69	T
MutationAssessor	Benign	1.7	L;.
MutationTaster	Benign	0.95	D;D;D;D;D
PrimateAI	Uncertain	0.53	T
PROVEAN	Uncertain	-2.4	N;D
REVEL	Benign	0.20
Sift	Uncertain	0.018	D;D
Sift4G	Uncertain	0.027	D;D
Polyphen		0.89	P;.
Vest4		0.74
MutPred		0.34		Loss of ubiquitination at K386 (P = 0.0141);.;
MVP		0.67
MPC		0.95
ClinPred		0.83	D
GERP RS		3.8
Varity_R		0.54

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

Publications

LitVar

Other links and lift over

dbSNP: rs1356164803; hg19: chr1-204101322;