rs1531100

Positions:

• chr17-17561514-G-A
• chr17-17561514-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+15406C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.447 in 152,010 control chromosomes in the GnomAD database, including 15,764 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 0.45 (15764 hom., cov: 31)
• Consequence: PEMT NM_148172.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.898

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	Protein	UniProt
PEMT	NM_148172.3	c.204+15406C>T		intron_variant		ENST00000255389.10	NP_680477.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PEMT	ENST00000255389.10	c.204+15406C>T		intron_variant		1	NM_148172.3	ENSP00000255389

Frequencies

GnomAD3 genomes AF: 0.447 AC: 67954 AN: 151892 Hom.: 15762 Cov.: 31

Gnomad AFR AF: 0.337

Gnomad AMI AF: 0.499

Gnomad AMR AF: 0.471

Gnomad ASJ AF: 0.538

Gnomad EAS AF: 0.311

Gnomad SAS AF: 0.331

Gnomad FIN AF: 0.473

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.518

Gnomad OTH AF: 0.446

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

GnomAD4 genome AF: 0.447 AC: 67970 AN: 152010 Hom.: 15764 Cov.: 31 AF XY: 0.442 AC XY: 32840 AN XY: 74308

Gnomad4 AFR AF: 0.336

Gnomad4 AMR AF: 0.472

Gnomad4 ASJ AF: 0.538

Gnomad4 EAS AF: 0.311

Gnomad4 SAS AF: 0.330

Gnomad4 FIN AF: 0.473

Gnomad4 NFE AF: 0.518

Gnomad4 OTH AF: 0.442

Alfa AF: 0.433 Hom.: 2552

Bravo AF: 0.442

Asia WGS AF: 0.326 AC: 1133 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	0.45
DANN	Benign	0.77

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: rs1531100; hg19: chr17-17464828;