11-68120912-C-A

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP2

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

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

neurodevelopmental disorder with microcephaly, movement abnormalities, and seizures
Inheritance: AR Classification: STRONG, MODERATE, LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics

CHKA links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant in the gene, where a lot of missense mutations are associated with disease in ClinVar. The gene has 3 curated pathogenic missense variants (we use a threshold of 10). The gene has 0 curated benign missense variants. Gene score misZ: 1.0029 (below the threshold of 3.09). Trascript score misZ: -0.65357 (below the threshold of 3.09). GenCC associations: The gene is linked to neurodevelopmental disorder with microcephaly, movement abnormalities, and seizures.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001277.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CHKA	NM_001277.3	MANE Select	c.266G>T	p.Arg89Leu	missense	Exon 1 of 12	NP_001268.2
CHKA	NM_001376219.1		c.266G>T	p.Arg89Leu	missense	Exon 1 of 13	NP_001363148.1
CHKA	NM_212469.2		c.266G>T	p.Arg89Leu	missense	Exon 1 of 11	NP_997634.1	P35790-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CHKA	ENST00000265689.9	TSL:1 MANE Select	c.266G>T	p.Arg89Leu	missense	Exon 1 of 12	ENSP00000265689.4	P35790-1
CHKA	ENST00000356135.9	TSL:1	c.266G>T	p.Arg89Leu	missense	Exon 1 of 11	ENSP00000348454.4	P35790-2
CHKA	ENST00000931669.1		c.266G>T	p.Arg89Leu	missense	Exon 1 of 12	ENSP00000601728.1

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

GnomAD2 exomes

AF:

0.00000967

AC:

AN:

103456

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000178

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000830

AC:

AN:

1083774

Hom.:

Cov.:

AF XY:

0.00000951

AC XY:

AN XY:

526018

show subpopulations

African (AFR)

AF:

0.0000455

AC:

AN:

21958

American (AMR)

AF:

0.00

AC:

AN:

16324

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

12742

East Asian (EAS)

AF:

0.00

AC:

AN:

20924

South Asian (SAS)

AF:

0.00

AC:

AN:

34000

European-Finnish (FIN)

AF:

0.00

AC:

AN:

21338

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4230

European-Non Finnish (NFE)

AF:

0.00000768

AC:

AN:

911792

Other (OTH)

AF:

0.0000247

AC:

AN:

40466

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.453

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00000667

AC:

AN:

149860

Hom.:

Cov.:

AF XY:

0.0000137

AC XY:

AN XY:

73090

show subpopulations

African (AFR)

AF:

0.0000243

AC:

AN:

41218

American (AMR)

AF:

0.00

AC:

AN:

15096

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3434

East Asian (EAS)

AF:

0.00

AC:

AN:

5162

South Asian (SAS)

AF:

0.00

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9764

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67064

Other (OTH)

AF:

0.00

AC:

AN:

2060

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.00000756

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.26

BayesDel_addAF

Benign

-0.043

BayesDel_noAF

Benign

-0.30

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.24

Eigen

Benign

0.028

Eigen_PC

Benign

-0.046

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.76

M_CAP

Pathogenic

0.93

MetaRNN

Uncertain

0.58

MetaSVM

Benign

-0.87

MutationAssessor

Benign

0.81

PhyloP100

4.3

PrimateAI

Pathogenic

0.93

PROVEAN

Uncertain

-2.4

REVEL

Benign

0.15

Sift

Benign

0.037

Sift4G

Benign

0.063

Polyphen

0.90

Vest4

0.50

MutPred

0.41

Loss of MoRF binding (P = 0.0322)

MVP

0.60

MPC

1.3

ClinPred

0.83

GERP RS

1.8

PromoterAI

-0.024

Neutral

(source)

Varity_R

0.39

gMVP

0.58

Mutation Taster

=49/51

disease causing

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over