rs4646356

chr17-17567861-G-Achr17-17567861-G-C

Variant summary

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

The NM_148172.3(PEMT):c.204+9059C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.437 in 152,166 control chromosomes in the GnomAD database, including 15,306 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 0.44 (15306 hom., cov: 34)
• Consequence: PEMT NM_148172.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.798

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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.514 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PEMT	NM_148172.3	c.204+9059C>T		intron_variant		ENST00000255389.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PEMT	ENST00000255389.10	c.204+9059C>T		intron_variant		1	NM_148172.3

Frequencies

GnomAD3 genomes AF: 0.437 AC: 66494 AN: 152048 Hom.: 15304 Cov.: 34

Gnomad AFR AF: 0.303

Gnomad AMI AF: 0.501

Gnomad AMR AF: 0.466

Gnomad ASJ AF: 0.538

Gnomad EAS AF: 0.310

Gnomad SAS AF: 0.330

Gnomad FIN AF: 0.473

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.518

Gnomad OTH AF: 0.438

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

GnomAD4 genome AF: 0.437 AC: 66510 AN: 152166 Hom.: 15306 Cov.: 34 AF XY: 0.432 AC XY: 32164 AN XY: 74374

Gnomad4 AFR AF: 0.302

Gnomad4 AMR AF: 0.466

Gnomad4 ASJ AF: 0.538

Gnomad4 EAS AF: 0.310

Gnomad4 SAS AF: 0.329

Gnomad4 FIN AF: 0.473

Gnomad4 NFE AF: 0.518

Gnomad4 OTH AF: 0.434

Alfa AF: 0.461 Hom.: 2800

Bravo AF: 0.431

Asia WGS AF: 0.323 AC: 1123 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.21
Dann	Benign	0.91

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: rs4646356; hg19: chr17-17471175;