NM_148172.3:c.205-13749G>A

Variant names:

• chr17-17536144-C-T
• rs750546
• NM_148172.3:c.205-13749G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 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=-0.91).
• 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 rank	MANE	Protein	UniProt
PEMT	NM_148172.3	c.205-13749G>A		intron_variant	Intron 2 of 6	ENST00000255389.10	NP_680477.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PEMT	ENST00000255389.10	c.205-13749G>A		intron_variant	Intron 2 of 6	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

African (AFR) AF: 0.429 AC: 17819 AN: 41528

American (AMR) AF: 0.490 AC: 7498 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.505 AC: 1752 AN: 3470

East Asian (EAS) AF: 0.408 AC: 2108 AN: 5170

South Asian (SAS) AF: 0.332 AC: 1601 AN: 4828

European-Finnish (FIN) AF: 0.478 AC: 5059 AN: 10592

Middle Eastern (MID) AF: 0.517 AC: 152 AN: 294

European-Non Finnish (NFE) AF: 0.534 AC: 36326 AN: 67978

Other (OTH) AF: 0.485 AC: 1023 AN: 2110

Alfa AF: 0.520 Hom.: 76833

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
PhyloP100		-1.3
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: rs750546; hg19: chr17-17439458;