Genetic Variant CHKA:p.Arg89Leu (chr11-68120912-C-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_001277.3(CHKA):c.266G>T(p.Arg89Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000811 in 1,233,634 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000067 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000083 ( 0 hom. )

Consequence

CHKA
NM_001277.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.27

Variant links:

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]

CHKA links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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 rank	MANE	Protein	UniProt
CHKA	NM_001277.3 link	c.266G>T	p.Arg89Leu	missense_variant	Exon 1 of 12	ENST00000265689.9	NP_001268.2	P35790-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CHKA	ENST00000265689.9 link	c.266G>T	p.Arg89Leu	missense_variant	Exon 1 of 12	1	NM_001277.3	ENSP00000265689.4	P35790-1
CHKA	ENST00000356135.9 link	c.266G>T	p.Arg89Leu	missense_variant	Exon 1 of 11	1		ENSP00000348454.4	P35790-2
CHKA	ENST00000531341.1 link	c.-139G>T		upstream_gene_variant		3		ENSP00000435032.1	E9PM06

Frequencies

GnomAD3 genomes

AF:

0.00000667

AC:

AN:

149860

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000243

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000830

AC:

AN:

1083774

Hom.:

Cov.:

AF XY:

0.00000951

AC XY:

AN XY:

526018

show subpopulations

Gnomad4 AFR exome

AF:

0.0000455

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:

0.00000768

Gnomad4 OTH exome

AF:

0.0000247

GnomAD4 genome

AF:

0.00000667

AC:

AN:

149860

Hom.:

Cov.:

AF XY:

0.0000137

AC XY:

AN XY:

73090

show subpopulations

Gnomad4 AFR

AF:

0.0000243

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 21, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.266G>T (p.R89L) alteration is located in exon 1 (coding exon 1) of the CHKA gene. This alteration results from a G to T substitution at nucleotide position 266, causing the arginine (R) at amino acid position 89 to be replaced by a leucine (L). 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

0.26

BayesDel_addAF

Benign

-0.043

BayesDel_noAF

Benign

-0.30

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.24

T;.

Eigen

Benign

0.028

Eigen_PC

Benign

-0.046

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.76

T;T

M_CAP

Pathogenic

0.93

MetaRNN

Uncertain

0.58

D;D

MetaSVM

Benign

-0.87

MutationAssessor

Benign

0.81

L;L

PrimateAI

Pathogenic

0.93

PROVEAN

Uncertain

-2.4

N;N

REVEL

Benign

0.15

Sift

Benign

0.037

D;D

Sift4G

Benign

0.063

T;T

Polyphen

0.90

P;D

Vest4

0.50

MutPred

0.41

Loss of MoRF binding (P = 0.0322);Loss of MoRF binding (P = 0.0322);

MVP

0.60

MPC

1.3

ClinPred

0.83

GERP RS

1.8

Varity_R

0.39

gMVP

0.58

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over