NM_018208.4:c.519G>A

Variant names:

• chr1-204146764-C-T
• rs1657801830
• NM_018208.4:c.519G>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 3P and 2B. PM2 PP3 BP6_Moderate

The NM_018208.4(ETNK2):​c.519G>A​(p.Arg173Arg) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ETNK2 NM_018208.4 splice_region, synonymous
• Scores: Splicing: ADA: 0.9987
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.86
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF. No scorers claiming Uncertain. Scorers claiming Benign: max_spliceai.
• BP6: Variant 1-204146764-C-T is Benign according to our data. Variant chr1-204146764-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2618552.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018208.4. 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
	ETNK2	NM_018208.4	MANE Select	c.519G>A	p.Arg173Arg	splice_region synonymous	Exon 3 of 8	NP_060678.2	Q9NVF9-1
	ETNK2	NM_001297761.2		c.-16G>A		splice_region	Exon 2 of 7	NP_001284690.1	B7Z1G7
	ETNK2	NM_001297760.2		c.519G>A	p.Arg173Arg	splice_region synonymous	Exon 3 of 8	NP_001284689.1	Q9NVF9-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ETNK2	ENST00000367202.9	TSL:1 MANE Select	c.519G>A	p.Arg173Arg	splice_region synonymous	Exon 3 of 8	ENSP00000356170.4	Q9NVF9-1
	ETNK2	ENST00000452983.5	TSL:4	c.90G>A	p.Trp30*	stop_gained splice_region	Exon 2 of 5	ENSP00000398091.1	B7ZC34
	ETNK2	ENST00000367201.7	TSL:2	c.519G>A	p.Arg173Arg	splice_region synonymous	Exon 3 of 8	ENSP00000356169.3	Q9NVF9-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.054	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	20
DANN	Uncertain	1.0
Eigen	Pathogenic	0.80
Eigen_PC	Pathogenic	0.67
FATHMM_MKL	Benign	0.74	D
M_CAP	Benign	0.064	D
PhyloP100		1.9
GERP RS		4.4
PromoterAI		-0.024	Neutral
Mutation Taster		=56/44	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	1.0
dbscSNV1_RF	Pathogenic	0.89
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: rs1657801830; hg19: chr1-204115892;