12-101723803-T-C

Variant names:

• chr12-101723803-T-C
• rs79716906
• NM_020244.3:c.1021T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 5.93

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]

ACMG classification

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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHPT1	NM_020244.3	c.1021T>C	p.Phe341Leu	missense_variant	Exon 7 of 9	ENST00000229266.8	NP_064629.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHPT1	ENST00000229266.8	c.1021T>C	p.Phe341Leu	missense_variant	Exon 7 of 9	1	NM_020244.3	ENSP00000229266.3

Frequencies

GnomAD3 genomes AF: 0.00319 AC: 486 AN: 152220 Hom.: 8 Cov.: 32

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

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.: 70 Cov.: 23 AF XY: 0.00252 AC XY: 1758 AN XY: 696608

Gnomad4 AFR exome AF: 0.000129 AC: 4 AN: 31114

Gnomad4 AMR exome AF: 0.00478 AC: 208 AN: 43512

Gnomad4 ASJ exome AF: 0.00 AC: 0 AN: 25638

Gnomad4 EAS exome AF: 0.0553 AC: 2154 AN: 38944

Gnomad4 SAS exome AF: 0.00227 AC: 189 AN: 83294

Gnomad4 FIN exome AF: 0.00839 AC: 446 AN: 53190

Gnomad4 NFE exome AF: 0.000409 AC: 431 AN: 1053714

Gnomad4 Remaining exome AF: 0.00329 AC: 190 AN: 57802

GnomAD4 genome AF: 0.00318 AC: 484 AN: 152338 Hom.: 7 Cov.: 32 AF XY: 0.00372 AC XY: 277 AN XY: 74496

Gnomad4 AFR AF: 0.000289 AC: 0.0002886 AN: 0.0002886

Gnomad4 AMR AF: 0.00229 AC: 0.00228698 AN: 0.00228698

Gnomad4 ASJ AF: 0.00 AC: 0 AN: 0

Gnomad4 EAS AF: 0.0528 AC: 0.0528142 AN: 0.0528142

Gnomad4 SAS AF: 0.00269 AC: 0.00269374 AN: 0.00269374

Gnomad4 FIN AF: 0.00847 AC: 0.00847458 AN: 0.00847458

Gnomad4 NFE AF: 0.000779 AC: 0.000779068 AN: 0.000779068

Gnomad4 OTH AF: 0.00284 AC: 0.00284091 AN: 0.00284091

Alfa AF: 0.00272 Hom.: 23

Bravo AF: 0.00345

ExAC AF: 0.00633 AC: 768

Asia WGS AF: 0.0190 AC: 68 AN: 3478

EpiCase AF: 0.000274

EpiControl AF: 0.000239

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 22, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.92
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Uncertain	0.020
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.13	T;.
Eigen	Uncertain	0.58
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.93	D;.
MetaRNN	Benign	0.0090	T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Uncertain	2.4	M;.
PrimateAI	Uncertain	0.67	T
PROVEAN	Pathogenic	-5.5	D;D
REVEL	Uncertain	0.45
Sift	Benign	0.047	D;D
Sift4G	Benign	0.066	T;T
Polyphen		1.0	D;D
Vest4		0.44
MutPred		0.53		Gain of catalytic residue at F336 (P = 0.0077);Gain of catalytic residue at F336 (P = 0.0077);
MVP		0.74
MPC		0.38
ClinPred		0.085	T
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

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

LitVar

Other links and lift over

dbSNP: rs79716906; hg19: chr12-102117581; COSMIC: COSV107212604; COSMIC: COSV107212604;