Variant chr17-17522317-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_148172.3(PEMT):c.283G>A(p.Val95Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.413 in 1,612,294 control chromosomes in the GnomAD database, including 147,564 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.33 ( 9812 hom., cov: 31)

Exomes 𝑓: 0.42 ( 137752 hom. )

Consequence

PEMT
NM_148172.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0210

Variant links:

Genes affected

PEMT (HGNC:8830): (phosphatidylethanolamine N-methyltransferase) Phosphatidylcholine (PC) is the most abundant mammalian phospholipid. This gene encodes an enzyme which converts phosphatidylethanolamine to phosphatidylcholine by sequential methylation in the liver. Another distinct synthetic pathway in nucleated cells converts intracellular choline to phosphatidylcholine by a three-step process. The protein isoforms encoded by this gene localize to the endoplasmic reticulum and mitochondria-associated membranes. Alternate splicing of this gene results in multiple transcript variants encoding different isoforms. [provided by RefSeq, May 2012]

PEMT links:

PEMT (HGNC:):

PEMT links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=3.1906366E-4).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.457 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PEMT	NM_148172.3 linkuse as main transcript	c.283G>A	p.Val95Ile	missense_variant	3/7	ENST00000255389.10	NP_680477.1	Q9UBM1-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PEMT	ENST00000255389.10 linkuse as main transcript	c.283G>A	p.Val95Ile	missense_variant	3/7	1	NM_148172.3	ENSP00000255389.5		Q9UBM1-2

Frequencies

GnomAD3 genomes

AF:

0.327

AC:

49633

AN:

151926

Hom.:

9816

Cov.:

show subpopulations

Gnomad AFR

AF:

0.125

Gnomad AMI

AF:

0.492

Gnomad AMR

AF:

0.321

Gnomad ASJ

AF:

0.358

Gnomad EAS

AF:

0.0981

Gnomad SAS

AF:

0.201

Gnomad FIN

AF:

0.400

Gnomad MID

AF:

0.408

Gnomad NFE

AF:

0.461

Gnomad OTH

AF:

0.338

GnomAD3 exomes

AF:

0.340

AC:

85115

AN:

250372

Hom.:

16846

AF XY:

0.345

AC XY:

46703

AN XY:

135494

show subpopulations

Gnomad AFR exome

AF:

0.112

Gnomad AMR exome

AF:

0.237

Gnomad ASJ exome

AF:

0.372

Gnomad EAS exome

AF:

0.0940

Gnomad SAS exome

AF:

0.211

Gnomad FIN exome

AF:

0.412

Gnomad NFE exome

AF:

0.459

Gnomad OTH exome

AF:

0.399

GnomAD4 exome

AF:

0.422

AC:

615538

AN:

1460250

Hom.:

137752

Cov.:

AF XY:

0.416

AC XY:

302262

AN XY:

726450

show subpopulations

Gnomad4 AFR exome

AF:

0.111

Gnomad4 AMR exome

AF:

0.249

Gnomad4 ASJ exome

AF:

0.368

Gnomad4 EAS exome

AF:

0.141

Gnomad4 SAS exome

AF:

0.212

Gnomad4 FIN exome

AF:

0.414

Gnomad4 NFE exome

AF:

0.468

Gnomad4 OTH exome

AF:

0.390

GnomAD4 genome

AF:

0.326

AC:

49623

AN:

152044

Hom.:

9812

Cov.:

AF XY:

0.321

AC XY:

23814

AN XY:

74276

show subpopulations

Gnomad4 AFR

AF:

0.124

Gnomad4 AMR

AF:

0.321

Gnomad4 ASJ

AF:

0.358

Gnomad4 EAS

AF:

0.0978

Gnomad4 SAS

AF:

0.201

Gnomad4 FIN

AF:

0.400

Gnomad4 NFE

AF:

0.461

Gnomad4 OTH

AF:

0.336

Alfa

AF:

0.418

Hom.:

29672

Bravo

AF:

0.313

TwinsUK

AF:

0.476

AC:

1766

ALSPAC

AF:

0.488

AC:

1881

ESP6500AA

AF:

0.130

AC:

574

ESP6500EA

AF:

0.451

AC:

3877

ExAC

AF:

0.342

AC:

41557

Asia WGS

AF:

0.174

AC:

604

AN:

3478

EpiCase

AF:

0.443

EpiControl

AF:

0.454

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.80

BayesDel_noAF

Benign

-0.78

CADD

Benign

0.70

DANN

Benign

0.75

DEOGEN2

Benign

0.060

T;T;.;.;.

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.0098

LIST_S2

Benign

0.77

.;T;T;T;T

MetaRNN

Benign

0.00032

T;T;T;T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

-0.36

N;N;.;.;.

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.27

N;N;N;N;N

REVEL

Benign

0.0090

Sift

Benign

0.67

T;T;T;T;T

Sift4G

Benign

0.74

T;T;T;T;T

Polyphen

0.0010

B;B;.;B;.

Vest4

0.024

MPC

0.065

ClinPred

0.00055

GERP RS

-5.1

Varity_R

0.017

gMVP

0.27

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over