Genetic Variant NM_020244.3:c.1021T>C (chr12-101723803-T-C) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_020244.3(CHPT1):c.1021T>C(p.Phe341Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00266 in 1,544,868 control chromosomes in the GnomAD database, including 77 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0032 ( 7 hom., cov: 32)

Exomes 𝑓: 0.0026 ( 70 hom. )

Consequence

CHPT1
NM_020244.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 5.93

Publications

7 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: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008994997).

BP6

Variant 12-101723803-T-C is Benign according to our data. Variant chr12-101723803-T-C is described in ClinVar as Benign. ClinVar VariationId is 782716.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAdExome4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0534 is higher than 0.05.

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.1021T>C	p.Phe341Leu	missense	Exon 7 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.1021T>C	p.Phe341Leu	missense	Exon 7 of 9	ENSP00000229266.3	Q8WUD6-1
CHPT1	ENST00000552215.5	TSL:1	n.*391T>C		non_coding_transcript_exon	Exon 8 of 9	ENSP00000448831.1	H0YI84
CHPT1	ENST00000552215.5	TSL:1	n.*391T>C		3_prime_UTR	Exon 8 of 9	ENSP00000448831.1	H0YI84

Frequencies

GnomAD3 genomes

AF:

0.00319

AC:

486

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000289

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00229

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0529

Gnomad SAS

AF:

0.00269

Gnomad FIN

AF:

0.00847

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000779

Gnomad OTH

AF:

0.00335

GnomAD2 exomes

AF:

0.00655

AC:

1597

AN:

243758

AF XY:

0.00619

show subpopulations

Gnomad AFR exome

AF:

0.000190

Gnomad AMR exome

AF:

0.00459

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0595

Gnomad FIN exome

AF:

0.00908

Gnomad NFE exome

AF:

0.00121

Gnomad OTH exome

AF:

0.00319

GnomAD4 exome

AF:

0.00260

AC:

3626

AN:

1392530

Hom.:

Cov.:

AF XY:

0.00252

AC XY:

1758

AN XY:

696608

show subpopulations

African (AFR)

AF:

0.000129

AC:

AN:

31114

American (AMR)

AF:

0.00478

AC:

208

AN:

43512

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25638

East Asian (EAS)

AF:

0.0553

AC:

2154

AN:

38944

South Asian (SAS)

AF:

0.00227

AC:

189

AN:

83294

European-Finnish (FIN)

AF:

0.00839

AC:

446

AN:

53190

Middle Eastern (MID)

AF:

0.000752

AC:

AN:

5322

European-Non Finnish (NFE)

AF:

0.000409

AC:

431

AN:

1053714

Other (OTH)

AF:

0.00329

AC:

190

AN:

57802

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

158

316

475

633

791

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

150

200

250

<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:

0.00318

AC:

484

AN:

152338

Hom.:

Cov.:

AF XY:

0.00372

AC XY:

277

AN XY:

74496

show subpopulations

African (AFR)

AF:

0.000289

AC:

AN:

41580

American (AMR)

AF:

0.00229

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.0528

AC:

274

AN:

5188

South Asian (SAS)

AF:

0.00269

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00847

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000779

AC:

AN:

68030

Other (OTH)

AF:

0.00284

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

115

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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:

0.00272

Hom.:

Bravo

AF:

0.00345

ExAC

AF:

0.00633

AC:

768

Asia WGS

AF:

0.0190

AC:

AN:

3478

EpiCase

AF:

0.000274

EpiControl

AF:

0.000239

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.92

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Uncertain

0.020

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.13

Eigen

Uncertain

0.58

Eigen_PC

Uncertain

0.55

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.93

MetaRNN

Benign

0.0090

MetaSVM

Benign

-0.96

MutationAssessor

Uncertain

2.4

PhyloP100

5.9

PrimateAI

Uncertain

0.67

PROVEAN

Pathogenic

-5.5

REVEL

Uncertain

0.45

Sift

Benign

0.047

Sift4G

Benign

0.066

Polyphen

1.0

Vest4

0.44

MutPred

0.53

Gain of catalytic residue at F336 (P = 0.0077)

MVP

0.74

MPC

0.38

ClinPred

0.085

GERP RS

5.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.52

gMVP

0.60

Mutation Taster

=91/9

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