chr17-17529142-C-T

Variant names:

• chr17-17529142-C-T
• rs16961845
• NM_148172.3:c.205-6747G>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.205-6747G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.132 in 152,240 control chromosomes in the GnomAD database, including 2,376 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 0.13 (2376 hom., cov: 33)
• Consequence: PEMT NM_148172.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0230
• Publications: 6 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.313 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PEMT	NM_148172.3	MANE Select	c.205-6747G>A		intron	N/A	NP_680477.1	Q9UBM1-2
	PEMT	NM_001267552.2		c.205-6747G>A		intron	N/A	NP_001254481.1	Q9UBM1-3
	PEMT	NM_001267551.2		c.139-6747G>A		intron	N/A	NP_001254480.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PEMT	ENST00000255389.10	TSL:1 MANE Select	c.205-6747G>A		intron	N/A	ENSP00000255389.5	Q9UBM1-2
	PEMT	ENST00000395782.5	TSL:1	c.94-6747G>A		intron	N/A	ENSP00000379128.1	Q9UBM1-1
	PEMT	ENST00000395783.5	TSL:1	c.94-6747G>A		intron	N/A	ENSP00000379129.1	Q9UBM1-1

Frequencies

GnomAD3 genomes AF: 0.132 AC: 20047 AN: 152122 Hom.: 2376 Cov.: 33

Gnomad AFR AF: 0.318

Gnomad AMI AF: 0.0274

Gnomad AMR AF: 0.0686

Gnomad ASJ AF: 0.0617

Gnomad EAS AF: 0.00365

Gnomad SAS AF: 0.0474

Gnomad FIN AF: 0.0812

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0621

Gnomad OTH AF: 0.120

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

GnomAD4 genome AF: 0.132 AC: 20070 AN: 152240 Hom.: 2376 Cov.: 33 AF XY: 0.129 AC XY: 9600 AN XY: 74446

African (AFR) AF: 0.317 AC: 13166 AN: 41496

American (AMR) AF: 0.0685 AC: 1048 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.0617 AC: 214 AN: 3468

East Asian (EAS) AF: 0.00366 AC: 19 AN: 5188

South Asian (SAS) AF: 0.0472 AC: 228 AN: 4826

European-Finnish (FIN) AF: 0.0812 AC: 862 AN: 10620

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.0620 AC: 4219 AN: 68012

Other (OTH) AF: 0.123 AC: 260 AN: 2114

Alfa AF: 0.105 Hom.: 574

Bravo AF: 0.138

Asia WGS AF: 0.0670 AC: 234 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.6
DANN	Benign	0.59
PhyloP100		0.023
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: rs16961845; hg19: chr17-17432456; COSMIC: COSV55133362;