rs759511552

Variant names:

• chr11-68064604-C-G
• rs759511552
• NM_001277.3:c.1153G>C

Your query was ambiguous. Multiple possible variants found:

• chr11-68064604-C-G
• chr11-68064604-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001277.3(CHKA):​c.1153G>C​(p.Ala385Pro) variant causes a missense 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. 15/21 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. A385T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CHKA NM_001277.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.39

Genes affected

CHKA (HGNC:1937): (choline kinase alpha) The major pathway for the biosynthesis of phosphatidylcholine occurs via the CDP-choline pathway. The protein encoded by this gene is the initial enzyme in the sequence and may play a regulatory role. The encoded protein also catalyzes the phosphorylation of ethanolamine. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.39461547).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHKA	NM_001277.3	c.1153G>C	p.Ala385Pro	missense_variant	Exon 10 of 12	ENST00000265689.9	NP_001268.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHKA	ENST00000265689.9	c.1153G>C	p.Ala385Pro	missense_variant	Exon 10 of 12	1	NM_001277.3	ENSP00000265689.4
CHKA	ENST00000356135.9	c.1099G>C	p.Ala367Pro	missense_variant	Exon 9 of 11	1		ENSP00000348454.4
CHKA	ENST00000525155.5	n.169G>C		non_coding_transcript_exon_variant	Exon 3 of 6	5		ENSP00000432631.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Benign	0.0042	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.19	T;.
Eigen	Benign	-0.11
Eigen_PC	Benign	0.044
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.85	D;D
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.39	T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.6	L;.
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-1.0	N;N
REVEL	Benign	0.20
Sift	Benign	0.24	T;T
Sift4G	Benign	0.17	T;T
Polyphen		0.24	B;B
Vest4		0.52
MutPred		0.55		Loss of catalytic residue at A385 (P = 0.0464);.;
MVP		0.49
MPC		0.86
ClinPred		0.75	D
GERP RS		4.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.38
gMVP		0.83

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: rs759511552; hg19: chr11-67832071;