Genetic Variant NM_020244.3:c.281A>G (chr12-101714097-A-G) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_020244.3(CHPT1):c.281A>G(p.Tyr94Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000035 in 1,599,800 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000035 ( 1 hom. )

Consequence

CHPT1
NM_020244.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.657

Publications

1 publications found

Variant links:

Genes affected

CHPT1 (HGNC:17852): (choline phosphotransferase 1) Enables diacylglycerol cholinephosphotransferase activity. Involved in phosphatidylcholine biosynthetic process and platelet activating factor biosynthetic process. Predicted to be located in Golgi membrane. Predicted to be active in Golgi apparatus and endoplasmic reticulum membrane. [provided by Alliance of Genome Resources, Apr 2022]

CHPT1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3670593).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020244.3. 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
	CHPT1	NM_020244.3	MANE Select	c.281A>G	p.Tyr94Cys	missense	Exon 2 of 9	NP_064629.2	Q8WUD6-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CHPT1	ENST00000229266.8	TSL:1 MANE Select	c.281A>G	p.Tyr94Cys	missense	Exon 2 of 9	ENSP00000229266.3	Q8WUD6-1
CHPT1	ENST00000552215.5	TSL:1	n.176A>G		non_coding_transcript_exon	Exon 2 of 9	ENSP00000448831.1	H0YI84
CHPT1	ENST00000868508.1		c.281A>G	p.Tyr94Cys	missense	Exon 2 of 10	ENSP00000538567.1

Frequencies

GnomAD3 genomes

AF:

0.0000328

AC:

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000163

AC:

AN:

244940

AF XY:

0.00000756

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:

0.0000358

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000352

AC:

AN:

1447580

Hom.:

Cov.:

AF XY:

0.0000291

AC XY:

AN XY:

720520

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32864

American (AMR)

AF:

0.00

AC:

AN:

42958

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25758

East Asian (EAS)

AF:

0.00

AC:

AN:

39578

South Asian (SAS)

AF:

0.0000119

AC:

AN:

84310

European-Finnish (FIN)

AF:

0.0000188

AC:

AN:

53298

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5728

European-Non Finnish (NFE)

AF:

0.0000435

AC:

AN:

1103190

Other (OTH)

AF:

0.0000167

AC:

AN:

59896

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

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:

0.0000328

AC:

AN:

152220

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74360

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41462

American (AMR)

AF:

0.00

AC:

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5194

South Asian (SAS)

AF:

0.00

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000735

AC:

AN:

68036

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

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:

0.000213

Hom.:

Bravo

AF:

0.0000264

ExAC

AF:

0.0000247

AC:

ClinVar

ClinVar submissions as Germline

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

0.071

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.43

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.025

Eigen

Benign

-0.45

Eigen_PC

Benign

-0.48

FATHMM_MKL

Benign

0.70

LIST_S2

Uncertain

0.86

M_CAP

Benign

0.014

MetaRNN

Benign

0.37

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.90

PhyloP100

0.66

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-1.5

REVEL

Benign

0.15

Sift

Benign

0.17

Sift4G

Benign

0.17

Polyphen

0.75

Vest4

0.45

MVP

0.54

MPC

0.86

ClinPred

0.17

GERP RS

-1.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.064

gMVP

0.41

Mutation Taster

=83/17

polymorphism

(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

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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