Genetic Variant NM_020244.3:c.418A>C (chr12-101714234-A-C) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_020244.3(CHPT1):c.418A>C(p.Thr140Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00000907 in 1,432,724 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. T140A) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000091 ( 0 hom. )

Consequence

CHPT1
NM_020244.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.92

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:

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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;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.803

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.418A>C	p.Thr140Pro	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.418A>C	p.Thr140Pro	missense	Exon 2 of 9	ENSP00000229266.3	Q8WUD6-1
CHPT1	ENST00000552215.5	TSL:1	n.313A>C		non_coding_transcript_exon	Exon 2 of 9	ENSP00000448831.1	H0YI84
CHPT1	ENST00000868508.1		c.418A>C	p.Thr140Pro	missense	Exon 2 of 10	ENSP00000538567.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000443

AC:

AN:

225714

AF XY:

0.0000410

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:

0.0000938

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000907

AC:

AN:

1432724

Hom.:

Cov.:

AF XY:

0.00000843

AC XY:

AN XY:

711524

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31682

American (AMR)

AF:

0.00

AC:

AN:

36788

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24640

East Asian (EAS)

AF:

0.00

AC:

AN:

39408

South Asian (SAS)

AF:

0.00

AC:

AN:

80088

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52902

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5600

European-Non Finnish (NFE)

AF:

0.0000118

AC:

AN:

1102552

Other (OTH)

AF:

0.00

AC:

AN:

59064

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ExAC

AF:

0.0000741

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.69

BayesDel_addAF

Uncertain

0.071

BayesDel_noAF

Uncertain

0.060

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.14

Eigen

Pathogenic

0.69

Eigen_PC

Uncertain

0.65

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.96

M_CAP

Benign

0.020

MetaRNN

Pathogenic

0.80

MetaSVM

Benign

-0.57

MutationAssessor

Pathogenic

3.5

PhyloP100

6.9

PrimateAI

Uncertain

0.69

PROVEAN

Pathogenic

-5.3

REVEL

Uncertain

0.47

Sift

Uncertain

0.0060

Sift4G

Uncertain

0.0070

Polyphen

1.0

Vest4

0.73

MutPred

0.56

Gain of catalytic residue at A144 (P = 8e-04)

MVP

0.75

MPC

1.1

ClinPred

0.94

GERP RS

4.7

Varity_R

0.87

gMVP

0.88

Mutation Taster

=71/29

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

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over