17-17588763-G-T

Position:

• chr17-17588763-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.96+2768C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.331 in 152,090 control chromosomes in the GnomAD database, including 9,837 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 0.33 (9837 hom., cov: 33)
• Consequence: PEMT NM_148172.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.63

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=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.448 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PEMT	NM_148172.3	c.96+2768C>A		intron_variant		ENST00000255389.10	NP_680477.1
PEMT	NM_001267552.2	c.96+2768C>A		intron_variant			NP_001254481.1
PEMT	NM_001267551.2	c.30+2834C>A		intron_variant			NP_001254480.1
PEMT	XM_024450532.2	c.-16+3204C>A		intron_variant			XP_024306300.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PEMT	ENST00000255389.10	c.96+2768C>A		intron_variant		1	NM_148172.3	ENSP00000255389.5

Frequencies

GnomAD3 genomes AF: 0.331 AC: 50319 AN: 151972 Hom.: 9838 Cov.: 33

Gnomad AFR AF: 0.137

Gnomad AMI AF: 0.416

Gnomad AMR AF: 0.369

Gnomad ASJ AF: 0.400

Gnomad EAS AF: 0.0994

Gnomad SAS AF: 0.214

Gnomad FIN AF: 0.385

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.453

Gnomad OTH AF: 0.342

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

GnomAD4 genome AF: 0.331 AC: 50334 AN: 152090 Hom.: 9837 Cov.: 33 AF XY: 0.325 AC XY: 24184 AN XY: 74340

Gnomad4 AFR AF: 0.137

Gnomad4 AMR AF: 0.369

Gnomad4 ASJ AF: 0.400

Gnomad4 EAS AF: 0.0997

Gnomad4 SAS AF: 0.214

Gnomad4 FIN AF: 0.385

Gnomad4 NFE AF: 0.453

Gnomad4 OTH AF: 0.340

Alfa AF: 0.176 Hom.: 416

Bravo AF: 0.323

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.12
DANN	Benign	0.82

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4646343; hg19: chr17-17492077;