12-22643850-A-C

Position:

• chr12-22643850-A-C

Variant summary

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

The NM_018638.5(ETNK1):​c.244A>C​(p.Asn82His) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ETNK1 NM_018638.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.73

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 (HGNC:):

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
ETNK1	NM_018638.5	c.244A>C	p.Asn82His	missense_variant	2/8	ENST00000266517.9	NP_061108.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ETNK1	ENST00000266517.9	c.244A>C	p.Asn82His	missense_variant	2/8	1	NM_018638.5	ENSP00000266517.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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

May 06, 2024

The c.511A>C (p.N171H) alteration is located in exon 2 (coding exon 2) of the ETNK1 gene. This alteration results from a A to C substitution at nucleotide position 511, causing the asparagine (N) at amino acid position 171 to be replaced by a histidine (H). 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	Benign	0.11
BayesDel_addAF	Benign	-0.035	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.025	T;.
Eigen	Uncertain	0.21
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.81	T;T
M_CAP	Benign	0.010	T
MetaRNN	Uncertain	0.46	T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	1.7	L;L
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	-1.9	N;N
REVEL	Benign	0.28
Sift	Benign	0.14	T;T
Sift4G	Benign	0.13	T;D
Polyphen		0.33	B;.
Vest4		0.67
MutPred		0.48		Gain of catalytic residue at I168 (P = 8e-04);Gain of catalytic residue at I168 (P = 8e-04);
MVP		0.58
MPC		1.5
ClinPred		0.90	D
GERP RS		5.3
Varity_R		0.44
gMVP		0.63

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-22796784;