17-17536144-C-T

Position:

• chr17-17536144-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.205-13749G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.485 in 152,182 control chromosomes in the GnomAD database, including 18,182 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 0.49 (18182 hom., cov: 34)
• Consequence: PEMT NM_148172.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.30

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]

PEMT (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.53 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PEMT	NM_148172.3	c.205-13749G>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.205-13749G>A		intron_variant		1	NM_148172.3	ENSP00000255389.5

Frequencies

GnomAD3 genomes AF: 0.485 AC: 73751 AN: 152064 Hom.: 18171 Cov.: 34

Gnomad AFR AF: 0.429

Gnomad AMI AF: 0.518

Gnomad AMR AF: 0.490

Gnomad ASJ AF: 0.505

Gnomad EAS AF: 0.408

Gnomad SAS AF: 0.332

Gnomad FIN AF: 0.478

Gnomad MID AF: 0.509

Gnomad NFE AF: 0.534

Gnomad OTH AF: 0.485

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

GnomAD4 genome AF: 0.485 AC: 73810 AN: 152182 Hom.: 18182 Cov.: 34 AF XY: 0.479 AC XY: 35642 AN XY: 74408

Gnomad4 AFR AF: 0.429

Gnomad4 AMR AF: 0.490

Gnomad4 ASJ AF: 0.505

Gnomad4 EAS AF: 0.408

Gnomad4 SAS AF: 0.332

Gnomad4 FIN AF: 0.478

Gnomad4 NFE AF: 0.534

Gnomad4 OTH AF: 0.485

Alfa AF: 0.525 Hom.: 39259

Bravo AF: 0.485

Asia WGS AF: 0.366 AC: 1275 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.73
DANN	Benign	0.45

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: rs750546; hg19: chr17-17439458;