dbSNP rs2278952: PEMT:c.-19C>T (chr17-17582270-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000395783.5(PEMT):c.-19C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0589 in 985,342 control chromosomes in the GnomAD database, including 1,864 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.055 ( 315 hom., cov: 32)

Exomes 𝑓: 0.060 ( 1549 hom. )

Consequence

PEMT
ENST00000395783.5 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.359

Publications

8 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0838 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PEMT	NM_148172.3 link	c.97-5243C>T		intron_variant	Intron 1 of 6	ENST00000255389.10	NP_680477.1	Q9UBM1-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PEMT	ENST00000255389.10 link	c.97-5243C>T		intron_variant	Intron 1 of 6	1	NM_148172.3	ENSP00000255389.5		Q9UBM1-2

Frequencies

GnomAD3 genomes

AF:

0.0552

AC:

8402

AN:

152148

Hom.:

314

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0127

Gnomad AMI

AF:

0.0559

Gnomad AMR

AF:

0.0621

Gnomad ASJ

AF:

0.151

Gnomad EAS

AF:

0.0810

Gnomad SAS

AF:

0.0907

Gnomad FIN

AF:

0.0820

Gnomad MID

AF:

0.0475

Gnomad NFE

AF:

0.0658

Gnomad OTH

AF:

0.0645

GnomAD4 exome

AF:

0.0595

AC:

49607

AN:

833076

Hom.:

1549

Cov.:

AF XY:

0.0595

AC XY:

22902

AN XY:

384728

show subpopulations

African (AFR)

AF:

0.00665

AC:

105

AN:

15786

American (AMR)

AF:

0.0579

AC:

AN:

984

Ashkenazi Jewish (ASJ)

AF:

0.139

AC:

718

AN:

5152

East Asian (EAS)

AF:

0.0882

AC:

320

AN:

3630

South Asian (SAS)

AF:

0.0982

AC:

1616

AN:

16458

European-Finnish (FIN)

AF:

0.0599

AC:

AN:

284

Middle Eastern (MID)

AF:

0.0686

AC:

111

AN:

1618

European-Non Finnish (NFE)

AF:

0.0589

AC:

44904

AN:

761858

Other (OTH)

AF:

0.0644

AC:

1759

AN:

27306

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

2146

4292

6439

8585

10731

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2314

4628

6942

9256

11570

<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:

0.0552

AC:

8406

AN:

152266

Hom.:

315

Cov.:

AF XY:

0.0553

AC XY:

4117

AN XY:

74444

show subpopulations

African (AFR)

AF:

0.0127

AC:

527

AN:

41554

American (AMR)

AF:

0.0620

AC:

948

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.151

AC:

524

AN:

3472

East Asian (EAS)

AF:

0.0817

AC:

423

AN:

5176

South Asian (SAS)

AF:

0.0908

AC:

438

AN:

4824

European-Finnish (FIN)

AF:

0.0820

AC:

870

AN:

10614

Middle Eastern (MID)

AF:

0.0476

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0658

AC:

4475

AN:

68022

Other (OTH)

AF:

0.0643

AC:

136

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

411

822

1232

1643

2054

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

108

216

324

432

540

<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:

0.0674

Hom.:

578

Bravo

AF:

0.0516

Asia WGS

AF:

0.0670

AC:

232

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

1.2

(source)

DANN

Benign

0.81

PhyloP100

-0.36

PromoterAI

0.020

Neutral

(source)

Mutation Taster

=300/0

polymorphism (auto)

(source)

Splicing

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over