rs4646402

chr17-17517873-G-Cchr17-17517873-G-T

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.45

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=-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/exons	MANE	UniProt
PEMT	NM_148172.3	c.320+4407C>G		intron_variant		ENST00000255389.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PEMT	ENST00000255389.10	c.320+4407C>G		intron_variant		1	NM_148172.3

Frequencies

GnomAD3 genomes AF: 0.518 AC: 78652 AN: 151956 Hom.: 20956 Cov.: 33

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

Gnomad4 AFR exome AF: 0.453

Gnomad4 AMR exome AF: 0.436

Gnomad4 ASJ exome AF: 0.548

Gnomad4 EAS exome AF: 0.290

Gnomad4 SAS exome AF: 0.388

Gnomad4 FIN exome AF: 0.574

Gnomad4 NFE exome AF: 0.594

Gnomad4 OTH exome AF: 0.548

GnomAD4 genome AF: 0.517 AC: 78683 AN: 152074 Hom.: 20955 Cov.: 33 AF XY: 0.511 AC XY: 38007 AN XY: 74338

Gnomad4 AFR AF: 0.463

Gnomad4 AMR AF: 0.448

Gnomad4 ASJ AF: 0.550

Gnomad4 EAS AF: 0.301

Gnomad4 SAS AF: 0.367

Gnomad4 FIN AF: 0.569

Gnomad4 NFE AF: 0.583

Gnomad4 OTH AF: 0.523

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
Dann	Benign	0.23

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: rs4646402; hg19: chr17-17421187; COSMIC: COSV55133286;