17-17516904-T-G

Variant names:

• chr17-17516904-T-G
• rs4244593
• NM_148172.3:c.321-4250A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_148172.3(PEMT):​c.321-4250A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.624 in 151,908 control chromosomes in the GnomAD database, including 30,484 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 0.62 (30484 hom., cov: 31)
• Consequence: PEMT NM_148172.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.548
• Publications: 14 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.773 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PEMT	NM_148172.3	c.321-4250A>C		intron_variant	Intron 3 of 6	ENST00000255389.10	NP_680477.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PEMT	ENST00000255389.10	c.321-4250A>C		intron_variant	Intron 3 of 6	1	NM_148172.3	ENSP00000255389.5

Frequencies

GnomAD3 genomes AF: 0.624 AC: 94734 AN: 151788 Hom.: 30446 Cov.: 31

Gnomad AFR AF: 0.780

Gnomad AMI AF: 0.551

Gnomad AMR AF: 0.548

Gnomad ASJ AF: 0.564

Gnomad EAS AF: 0.508

Gnomad SAS AF: 0.379

Gnomad FIN AF: 0.570

Gnomad MID AF: 0.564

Gnomad NFE AF: 0.586

Gnomad OTH AF: 0.603

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

GnomAD4 genome AF: 0.624 AC: 94834 AN: 151908 Hom.: 30484 Cov.: 31 AF XY: 0.617 AC XY: 45811 AN XY: 74234

African (AFR) AF: 0.780 AC: 32332 AN: 41450

American (AMR) AF: 0.548 AC: 8373 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.564 AC: 1956 AN: 3470

East Asian (EAS) AF: 0.508 AC: 2609 AN: 5138

South Asian (SAS) AF: 0.378 AC: 1820 AN: 4820

European-Finnish (FIN) AF: 0.570 AC: 6005 AN: 10528

Middle Eastern (MID) AF: 0.579 AC: 169 AN: 292

European-Non Finnish (NFE) AF: 0.586 AC: 39789 AN: 67916

Other (OTH) AF: 0.607 AC: 1282 AN: 2112

Alfa AF: 0.593 Hom.: 99755

Bravo AF: 0.632

Asia WGS AF: 0.474 AC: 1650 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.28
DANN	Benign	0.41
PhyloP100		-0.55
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4244593; hg19: chr17-17420218; COSMIC: COSV55133267;