NM_018208.4:c.644T>C

Variant names:

• chr1-204141455-A-G
• NM_018208.4:c.644T>C

Variant summary

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

The NM_018208.4(ETNK2):​c.644T>C​(p.Leu215Pro) variant causes a missense, splice region change. The variant was absent in control chromosomes in GnomAD project. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ETNK2 NM_018208.4 missense, splice_region
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.89
• 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]

ERLNC1 (HGNC:41109): (estrogen receptor responsive lncRNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

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.644T>C	p.Leu215Pro	missense splice_region	Exon 4 of 8	NP_060678.2	Q9NVF9-1
	ETNK2	NM_001297760.2		c.644T>C	p.Leu215Pro	missense splice_region	Exon 4 of 8	NP_001284689.1	Q9NVF9-2
	ETNK2	NM_001297762.2		c.521T>C	p.Leu174Pro	missense splice_region	Exon 3 of 7	NP_001284691.1	Q9NVF9-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ETNK2	ENST00000367202.9	TSL:1 MANE Select	c.644T>C	p.Leu215Pro	missense splice_region	Exon 4 of 8	ENSP00000356170.4	Q9NVF9-1
	ERLNC1	ENST00000433869.1	TSL:1	n.48A>G		non_coding_transcript_exon	Exon 1 of 3
	ETNK2	ENST00000367201.7	TSL:2	c.644T>C	p.Leu215Pro	missense splice_region	Exon 4 of 8	ENSP00000356169.3	Q9NVF9-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 6.99e-7 AC: 1 AN: 1431054 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 708924

African (AFR) AF: 0.00 AC: 0 AN: 32754

American (AMR) AF: 0.00 AC: 0 AN: 38604

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25570

East Asian (EAS) AF: 0.00 AC: 0 AN: 38220

South Asian (SAS) AF: 0.00 AC: 0 AN: 82428

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51752

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5708

European-Non Finnish (NFE) AF: 9.12e-7 AC: 1 AN: 1096582

Other (OTH) AF: 0.00 AC: 0 AN: 59436

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Uncertain	0.047	T
BayesDel_noAF	Benign	-0.17
CADD	Uncertain	26
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.079	T
Eigen	Uncertain	0.64
Eigen_PC	Uncertain	0.65
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.47	T
M_CAP	Benign	0.061	D
MetaRNN	Uncertain	0.72	D
MetaSVM	Benign	-0.64	T
MutationAssessor	Benign	1.9	L
PhyloP100		4.9
PrimateAI	Uncertain	0.53	T
PROVEAN	Uncertain	-2.7	D
REVEL	Uncertain	0.38
Sift	Benign	0.16	T
Sift4G	Benign	0.10	T
Polyphen		1.0	D
Vest4		0.25
MutPred		0.66		Gain of disorder (P = 0.0056)
MVP		0.89
MPC		1.2
ClinPred		0.96	D
GERP RS		5.9
PromoterAI		-0.0054	Neutral
Varity_R		0.64
gMVP		0.86
Mutation Taster		=37/63	disease causing

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

hg19: chr1-204110583;