17-17549753-C-T

Variant names:

• chr17-17549753-C-T
• rs11656215
• NM_148172.3:c.204+27167G>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.204+27167G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.446 in 152,192 control chromosomes in the GnomAD database, including 15,757 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 (15757 hom., cov: 34)
• Consequence: PEMT NM_148172.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.50
• 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]

ENSG00000306320 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.516 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_148172.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PEMT	NM_148172.3	MANE Select	c.204+27167G>A		intron	N/A	NP_680477.1
	PEMT	NM_001267552.2		c.204+27167G>A		intron	N/A	NP_001254481.1
	PEMT	NM_001267551.2		c.138+27167G>A		intron	N/A	NP_001254480.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PEMT	ENST00000255389.10	TSL:1 MANE Select	c.204+27167G>A		intron	N/A	ENSP00000255389.5
	PEMT	ENST00000395782.5	TSL:1	c.93+27167G>A		intron	N/A	ENSP00000379128.1
	PEMT	ENST00000395783.5	TSL:1	c.93+27167G>A		intron	N/A	ENSP00000379129.1

Frequencies

GnomAD3 genomes AF: 0.447 AC: 67916 AN: 152074 Hom.: 15755 Cov.: 34

Gnomad AFR AF: 0.334

Gnomad AMI AF: 0.514

Gnomad AMR AF: 0.467

Gnomad ASJ AF: 0.515

Gnomad EAS AF: 0.309

Gnomad SAS AF: 0.324

Gnomad FIN AF: 0.476

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.521

Gnomad OTH AF: 0.447

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

GnomAD4 genome AF: 0.446 AC: 67942 AN: 152192 Hom.: 15757 Cov.: 34 AF XY: 0.442 AC XY: 32867 AN XY: 74412

African (AFR) AF: 0.333 AC: 13832 AN: 41512

American (AMR) AF: 0.467 AC: 7140 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.515 AC: 1787 AN: 3468

East Asian (EAS) AF: 0.309 AC: 1598 AN: 5170

South Asian (SAS) AF: 0.324 AC: 1565 AN: 4830

European-Finnish (FIN) AF: 0.476 AC: 5049 AN: 10604

Middle Eastern (MID) AF: 0.490 AC: 144 AN: 294

European-Non Finnish (NFE) AF: 0.521 AC: 35416 AN: 68000

Other (OTH) AF: 0.446 AC: 943 AN: 2112

Alfa AF: 0.497 Hom.: 31622

Bravo AF: 0.441

Asia WGS AF: 0.309 AC: 1076 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.013
DANN	Benign	0.36
PhyloP100		-1.5
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: rs11656215; hg19: chr17-17453067;