rs2278952

chr17-17582270-G-Achr17-17582270-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000395783.5(PEMT):c.-19C>T variant causes a 5 prime UTR 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.359

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
PEMT	NM_148172.3	c.97-5243C>T		intron_variant		ENST00000255389.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PEMT	ENST00000255389.10	c.97-5243C>T		intron_variant		1	NM_148172.3

Frequencies

GnomAD3 genomes AF: 0.0552 AC: 8402 AN: 152148 Hom.: 314 Cov.: 32

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.: 30 AF XY: 0.0595 AC XY: 22902 AN XY: 384728

Gnomad4 AFR exome AF: 0.00665

Gnomad4 AMR exome AF: 0.0579

Gnomad4 ASJ exome AF: 0.139

Gnomad4 EAS exome AF: 0.0882

Gnomad4 SAS exome AF: 0.0982

Gnomad4 FIN exome AF: 0.0599

Gnomad4 NFE exome AF: 0.0589

Gnomad4 OTH exome AF: 0.0644

GnomAD4 genome AF: 0.0552 AC: 8406 AN: 152266 Hom.: 315 Cov.: 32 AF XY: 0.0553 AC XY: 4117 AN XY: 74444

Gnomad4 AFR AF: 0.0127

Gnomad4 AMR AF: 0.0620

Gnomad4 ASJ AF: 0.151

Gnomad4 EAS AF: 0.0817

Gnomad4 SAS AF: 0.0908

Gnomad4 FIN AF: 0.0820

Gnomad4 NFE AF: 0.0658

Gnomad4 OTH AF: 0.0643

Alfa AF: 0.0702 Hom.: 500

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
Dann	Benign	0.81

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2278952; hg19: chr17-17485584;