Genetic Variant PEMT:c.320+4407C>G (chr17-17517873-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_148172.3(PEMT):c.320+4407C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.568 in 626,550 control chromosomes in the GnomAD database, including 102,477 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 0.52 ( 20955 hom., cov: 33)

Exomes 𝑓: 0.58 ( 81522 hom. )

Consequence

PEMT
NM_148172.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -4.45

Publications

2 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=-1.01).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.578 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PEMT	NM_148172.3 link	c.320+4407C>G		intron_variant	Intron 3 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.320+4407C>G		intron_variant	Intron 3 of 6	1	NM_148172.3	ENSP00000255389.5		Q9UBM1-2

Frequencies

GnomAD3 genomes

AF:

0.518

AC:

78652

AN:

151956

Hom.:

20956

Cov.:

show subpopulations

Gnomad AFR

AF:

0.464

Gnomad AMI

AF:

0.554

Gnomad AMR

AF:

0.448

Gnomad ASJ

AF:

0.550

Gnomad EAS

AF:

0.301

Gnomad SAS

AF:

0.368

Gnomad FIN

AF:

0.569

Gnomad MID

AF:

0.525

Gnomad NFE

AF:

0.583

Gnomad OTH

AF:

0.520

GnomAD4 exome

AF:

0.584

AC:

277104

AN:

474476

Hom.:

81522

AF XY:

0.584

AC XY:

130442

AN XY:

223370

show subpopulations

African (AFR)

AF:

0.453

AC:

4021

AN:

8872

American (AMR)

AF:

0.436

AC:

233

AN:

534

Ashkenazi Jewish (ASJ)

AF:

0.548

AC:

1592

AN:

2906

East Asian (EAS)

AF:

0.290

AC:

572

AN:

1974

South Asian (SAS)

AF:

0.388

AC:

3612

AN:

9308

European-Finnish (FIN)

AF:

0.574

AC:

101

AN:

176

Middle Eastern (MID)

AF:

0.506

AC:

483

AN:

954

European-Non Finnish (NFE)

AF:

0.594

AC:

258042

AN:

434344

Other (OTH)

AF:

0.548

AC:

8448

AN:

15408

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

5570

11140

16710

22280

27850

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9602

19204

28806

38408

48010

<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:

0.517

AC:

78683

AN:

152074

Hom.:

20955

Cov.:

AF XY:

0.511

AC XY:

38007

AN XY:

74338

show subpopulations

African (AFR)

AF:

0.463

AC:

19197

AN:

41468

American (AMR)

AF:

0.448

AC:

6844

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.550

AC:

1907

AN:

3470

East Asian (EAS)

AF:

0.301

AC:

1559

AN:

5174

South Asian (SAS)

AF:

0.367

AC:

1769

AN:

4816

European-Finnish (FIN)

AF:

0.569

AC:

6032

AN:

10594

Middle Eastern (MID)

AF:

0.537

AC:

158

AN:

294

European-Non Finnish (NFE)

AF:

0.583

AC:

39606

AN:

67946

Other (OTH)

AF:

0.523

AC:

1106

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1977

3955

5932

7910

9887

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

688

1376

2064

2752

3440

<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:

0.418

Hom.:

1143

Bravo

AF:

0.504

Asia WGS

AF:

0.369

AC:

1285

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.033

(source)

DANN

Benign

0.23

PhyloP100

-4.4

Mutation Taster

=100/0

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over