rs4646406

Positions:

• chr17-17513855-T-A
• chr17-17513855-T-C

Variant summary

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

The NM_148172.3(PEMT):​c.321-1201A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.434 in 151,884 control chromosomes in the GnomAD database, including 14,993 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 0.43 (14993 hom., cov: 31)
• Consequence: PEMT NM_148172.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.876

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.516 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PEMT	NM_148172.3	c.321-1201A>T		intron_variant		ENST00000255389.10	NP_680477.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PEMT	ENST00000255389.10	c.321-1201A>T		intron_variant		1	NM_148172.3	ENSP00000255389.5

Frequencies

GnomAD3 genomes AF: 0.434 AC: 65813 AN: 151766 Hom.: 14982 Cov.: 31

Gnomad AFR AF: 0.360

Gnomad AMI AF: 0.516

Gnomad AMR AF: 0.369

Gnomad ASJ AF: 0.405

Gnomad EAS AF: 0.122

Gnomad SAS AF: 0.232

Gnomad FIN AF: 0.501

Gnomad MID AF: 0.452

Gnomad NFE AF: 0.521

Gnomad OTH AF: 0.419

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.434 AC: 65863 AN: 151884 Hom.: 14993 Cov.: 31 AF XY: 0.427 AC XY: 31676 AN XY: 74252

Gnomad4 AFR AF: 0.361

Gnomad4 AMR AF: 0.369

Gnomad4 ASJ AF: 0.405

Gnomad4 EAS AF: 0.121

Gnomad4 SAS AF: 0.230

Gnomad4 FIN AF: 0.501

Gnomad4 NFE AF: 0.521

Gnomad4 OTH AF: 0.421

Alfa AF: 0.359 Hom.: 1025

Bravo AF: 0.421

Asia WGS AF: 0.240 AC: 836 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.074
DANN	Benign	0.43

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

Other links and lift over

dbSNP: rs4646406; hg19: chr17-17417169; COSMIC: COSV55133248;