rs16961845

Positions:

• chr17-17529142-C-T

Variant summary

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

The NM_148172.3(PEMT):​c.205-6747G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.132 in 152,240 control chromosomes in the GnomAD database, including 2,376 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 0.13 (2376 hom., cov: 33)
• Consequence: PEMT NM_148172.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0230

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.313 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PEMT	NM_148172.3	c.205-6747G>A		intron_variant		ENST00000255389.10	NP_680477.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PEMT	ENST00000255389.10	c.205-6747G>A		intron_variant		1	NM_148172.3	ENSP00000255389

Frequencies

GnomAD3 genomes AF: 0.132 AC: 20047 AN: 152122 Hom.: 2376 Cov.: 33

Gnomad AFR AF: 0.318

Gnomad AMI AF: 0.0274

Gnomad AMR AF: 0.0686

Gnomad ASJ AF: 0.0617

Gnomad EAS AF: 0.00365

Gnomad SAS AF: 0.0474

Gnomad FIN AF: 0.0812

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0621

Gnomad OTH AF: 0.120

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

GnomAD4 genome AF: 0.132 AC: 20070 AN: 152240 Hom.: 2376 Cov.: 33 AF XY: 0.129 AC XY: 9600 AN XY: 74446

Gnomad4 AFR AF: 0.317

Gnomad4 AMR AF: 0.0685

Gnomad4 ASJ AF: 0.0617

Gnomad4 EAS AF: 0.00366

Gnomad4 SAS AF: 0.0472

Gnomad4 FIN AF: 0.0812

Gnomad4 NFE AF: 0.0620

Gnomad4 OTH AF: 0.123

Alfa AF: 0.113 Hom.: 345

Bravo AF: 0.138

Asia WGS AF: 0.0670 AC: 234 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.6
DANN	Benign	0.59

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: rs16961845; hg19: chr17-17432456; COSMIC: COSV55133362;