chr17-17506246-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -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. 13/17 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

Publications

130 publications found

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 was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_148172.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
PEMT	NM_148172.3	MANE Select	c.634G>A	p.Val212Met	missense	Exon 6 of 7	NP_680477.1
PEMT	NM_001267552.2		c.665G>A	p.Ser222Asn	missense	Exon 7 of 8	NP_001254481.1
PEMT	NM_001267551.2		c.568G>A	p.Val190Met	missense	Exon 6 of 7	NP_001254480.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
PEMT	ENST00000255389.10	TSL:1 MANE Select	c.634G>A	p.Val212Met	missense	Exon 6 of 7	ENSP00000255389.5
PEMT	ENST00000395782.5	TSL:1	c.523G>A	p.Val175Met	missense	Exon 6 of 7	ENSP00000379128.1
PEMT	ENST00000395783.5	TSL:1	c.523G>A	p.Val175Met	missense	Exon 6 of 7	ENSP00000379129.1

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

GnomAD2 exomes

AF:

0.588

AC:

114871

AN:

195430

AF XY:

0.591

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 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

African (AFR)

AF:

0.372

AC:

12184

AN:

32724

American (AMR)

AF:

0.548

AC:

21942

AN:

40062

Ashkenazi Jewish (ASJ)

AF:

0.629

AC:

16018

AN:

25462

East Asian (EAS)

AF:

0.240

AC:

9167

AN:

38212

South Asian (SAS)

AF:

0.484

AC:

39465

AN:

81480

European-Finnish (FIN)

AF:

0.701

AC:

35242

AN:

50260

Middle Eastern (MID)

AF:

0.521

AC:

2980

AN:

5722

European-Non Finnish (NFE)

AF:

0.748

AC:

817192

AN:

1092206

Other (OTH)

AF:

0.652

AC:

38417

AN:

58944

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

12645

25290

37935

50580

63225

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19778

39556

59334

79112

98890

<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:

0.590

AC:

89804

AN:

152162

Hom.:

28593

Cov.:

AF XY:

0.585

AC XY:

43491

AN XY:

74394

show subpopulations

African (AFR)

AF:

0.390

AC:

16173

AN:

41522

American (AMR)

AF:

0.568

AC:

8686

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.624

AC:

2167

AN:

3470

East Asian (EAS)

AF:

0.187

AC:

963

AN:

5160

South Asian (SAS)

AF:

0.472

AC:

2279

AN:

4826

European-Finnish (FIN)

AF:

0.700

AC:

7426

AN:

10604

Middle Eastern (MID)

AF:

0.643

AC:

189

AN:

294

European-Non Finnish (NFE)

AF:

0.737

AC:

50067

AN:

67964

Other (OTH)

AF:

0.597

AC:

1261

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1770

3541

5311

7082

8852

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

734

1468

2202

2936

3670

<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:

0.683

Hom.:

165381

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

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Oct 15, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 17391797, 16051693, 29083408, 31695245)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.78

BayesDel_noAF

Benign

-0.54

CADD

Benign

(source)

DANN

Benign

0.80

Eigen

Benign

-0.31

Eigen_PC

Benign

-0.50

FATHMM_MKL

Benign

0.058

LIST_S2

Benign

0.29

MetaRNN

Benign

0.0000022

MetaSVM

Benign

-0.97

PhyloP100

0.091

PROVEAN

Benign

-0.55

REVEL

Benign

0.069

Sift

Benign

0.54

Sift4G

Benign

0.29

Vest4

0.040

ClinPred

0.021

GERP RS

2.2

Varity_R

0.10

Mutation Taster

=98/2

polymorphism (auto)

(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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over