17-17519040-C-T

Position:

• chr17-17519040-C-T

Variant summary

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

The ENST00000255389.10(PEMT):​c.320+3240G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.408 in 152,162 control chromosomes in the GnomAD database, including 13,751 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 0.41 (13746 hom., cov: 33)
  • Exomes 𝑓: 0.53 (5 hom.)
• Consequence: PEMT ENST00000255389.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.736

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 = 0.509 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PEMT	NM_148172.3	c.320+3240G>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.320+3240G>A		intron_variant		1	NM_148172.3	ENSP00000255389

Frequencies

GnomAD3 genomes AF: 0.408 AC: 62031 AN: 152004 Hom.: 13751 Cov.: 33

Gnomad AFR AF: 0.286

Gnomad AMI AF: 0.518

Gnomad AMR AF: 0.358

Gnomad ASJ AF: 0.399

Gnomad EAS AF: 0.117

Gnomad SAS AF: 0.230

Gnomad FIN AF: 0.498

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.514

Gnomad OTH AF: 0.404

GnomAD4 exome AF: 0.525 AC: 21 AN: 40 Hom.: 5 Cov.: 0 AF XY: 0.571 AC XY: 16 AN XY: 28

Gnomad4 AFR exome AF: 0.500

Gnomad4 FIN exome AF: 0.667

Gnomad4 NFE exome AF: 0.500

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.408 AC: 62042 AN: 152122 Hom.: 13746 Cov.: 33 AF XY: 0.402 AC XY: 29862 AN XY: 74368

Gnomad4 AFR AF: 0.285

Gnomad4 AMR AF: 0.358

Gnomad4 ASJ AF: 0.399

Gnomad4 EAS AF: 0.117

Gnomad4 SAS AF: 0.229

Gnomad4 FIN AF: 0.498

Gnomad4 NFE AF: 0.514

Gnomad4 OTH AF: 0.406

Alfa AF: 0.473 Hom.: 4922

Bravo AF: 0.391

Asia WGS AF: 0.235 AC: 816 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	0.18
DANN	Benign	0.39

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: rs1108579; hg19: chr17-17422354;