Variant 17-17506246-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_148172.3(PEMT):c.634G>A(p.Val212Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.686 in 1,577,234 control chromosomes in the GnomAD database, including 385,160 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.59 ( 28593 hom., cov: 34)

Exomes 𝑓: 0.70 ( 356567 hom. )

Consequence

PEMT
NM_148172.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.0910

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:

ENSG00000286430 (HGNC:):

ENSG00000286430 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=2.2130116E-6).

BP6

Variant 17-17506246-C-T is Benign according to our data. Variant chr17-17506246-C-T is described in ClinVar as [Benign]. Clinvar id is 1279483.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.731 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PEMT	NM_148172.3 link	c.634G>A	p.Val212Met	missense_variant	6/7	ENST00000255389.10	NP_680477.1	Q9UBM1-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PEMT	ENST00000255389.10 link	c.634G>A	p.Val212Met	missense_variant	6/7	1	NM_148172.3	ENSP00000255389.5		Q9UBM1-2

Frequencies

GnomAD3 genomes

AF:

0.590

AC:

89759

AN:

152044

Hom.:

28586

Cov.:

show subpopulations

Gnomad AFR

AF:

0.390

Gnomad AMI

AF:

0.652

Gnomad AMR

AF:

0.567

Gnomad ASJ

AF:

0.624

Gnomad EAS

AF:

0.187

Gnomad SAS

AF:

0.473

Gnomad FIN

AF:

0.700

Gnomad MID

AF:

0.636

Gnomad NFE

AF:

0.737

Gnomad OTH

AF:

0.598

GnomAD3 exomes

AF:

0.588

AC:

114871

AN:

195430

Hom.:

36466

AF XY:

0.591

AC XY:

62099

AN XY:

105050

show subpopulations

Gnomad AFR exome

AF:

0.371

Gnomad AMR exome

AF:

0.539

Gnomad ASJ exome

AF:

0.629

Gnomad EAS exome

AF:

0.174

Gnomad SAS exome

AF:

0.474

Gnomad FIN exome

AF:

0.701

Gnomad NFE exome

AF:

0.719

Gnomad OTH exome

AF:

0.629

GnomAD4 exome

AF:

0.697

AC:

992607

AN:

1425072

Hom.:

356567

Cov.:

AF XY:

0.691

AC XY:

487337

AN XY:

705752

show subpopulations

Gnomad4 AFR exome

AF:

0.372

Gnomad4 AMR exome

AF:

0.548

Gnomad4 ASJ exome

AF:

0.629

Gnomad4 EAS exome

AF:

0.240

Gnomad4 SAS exome

AF:

0.484

Gnomad4 FIN exome

AF:

0.701

Gnomad4 NFE exome

AF:

0.748

Gnomad4 OTH exome

AF:

0.652

GnomAD4 genome

AF:

0.590

AC:

89804

AN:

152162

Hom.:

28593

Cov.:

AF XY:

0.585

AC XY:

43491

AN XY:

74394

show subpopulations

Gnomad4 AFR

AF:

0.390

Gnomad4 AMR

AF:

0.568

Gnomad4 ASJ

AF:

0.624

Gnomad4 EAS

AF:

0.187

Gnomad4 SAS

AF:

0.472

Gnomad4 FIN

AF:

0.700

Gnomad4 NFE

AF:

0.737

Gnomad4 OTH

AF:

0.597

Alfa

AF:

0.691

Hom.:

87443

Bravo

AF:

0.572

TwinsUK

AF:

0.752

AC:

2788

ALSPAC

AF:

0.764

AC:

2943

ESP6500AA

AF:

0.406

AC:

1784

ESP6500EA

AF:

0.723

AC:

6195

ExAC

AF:

0.551

AC:

64902

Asia WGS

AF:

0.379

AC:

1320

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 15, 2018	This variant is associated with the following publications: (PMID: 17391797, 16051693, 29083408, 31695245) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.78

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Benign

0.80

Eigen

Benign

-0.31

Eigen_PC

Benign

-0.50

FATHMM_MKL

Benign

0.058

LIST_S2

Benign

0.29

T;T

MetaRNN

Benign

0.0000022

T;T

MetaSVM

Benign

-0.97

PROVEAN

Benign

-0.55

N;N

REVEL

Benign

0.069

Sift

Benign

0.54

T;T

Sift4G

Benign

0.29

T;T

Vest4

0.040

ClinPred

0.021

GERP RS

2.2

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over