Genetic Variant NM_020244.3:c.571G>A (chr12-101716735-G-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_020244.3(CHPT1):c.571G>A(p.Val191Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000414 in 1,449,058 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

CHPT1
NM_020244.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.94

Publications

0 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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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.571G>A	p.Val191Ile	missense	Exon 4 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.571G>A	p.Val191Ile	missense	Exon 4 of 9	ENSP00000229266.3	Q8WUD6-1
CHPT1	ENST00000552215.5	TSL:1	n.466G>A		non_coding_transcript_exon	Exon 4 of 9	ENSP00000448831.1	H0YI84
CHPT1	ENST00000868508.1		c.571G>A	p.Val191Ile	missense	Exon 4 of 10	ENSP00000538567.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

243840

AF XY:

0.00

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000414

AC:

AN:

1449058

Hom.:

Cov.:

AF XY:

0.00000416

AC XY:

AN XY:

721096

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

33064

American (AMR)

AF:

0.00

AC:

AN:

42306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25868

East Asian (EAS)

AF:

0.00

AC:

AN:

39308

South Asian (SAS)

AF:

0.00

AC:

AN:

83992

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52820

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5728

European-Non Finnish (NFE)

AF:

0.00000542

AC:

AN:

1106134

Other (OTH)

AF:

0.00

AC:

AN:

59838

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00456380), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.383

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

Cov.:

Alfa

AF:

0.00

Hom.:

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

0.23

BayesDel_addAF

Benign

-0.030

BayesDel_noAF

Benign

-0.28

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.040

Eigen

Uncertain

0.67

Eigen_PC

Pathogenic

0.70

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.96

M_CAP

Benign

0.026

MetaRNN

Uncertain

0.67

MetaSVM

Benign

-0.78

MutationAssessor

Uncertain

2.6

PhyloP100

8.9

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-0.96

REVEL

Benign

0.20

Sift

Uncertain

0.0020

Sift4G

Benign

0.065

Polyphen

0.80

Vest4

0.64

MutPred

0.71

Gain of catalytic residue at Q195 (P = 0)

MVP

0.71

MPC

0.57

ClinPred

0.90

GERP RS

5.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.35

gMVP

0.61

Mutation Taster

=78/22

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over