17-17566005-C-G

Variant names:

• chr17-17566005-C-G
• rs4646361
• NM_148172.3:c.204+10915G>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.204+10915G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.066 in 152,274 control chromosomes in the GnomAD database, including 857 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 0.066 (857 hom., cov: 33)
• Consequence: PEMT NM_148172.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.14
• Publications: 3 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.19 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+10915G>C		intron	N/A	NP_680477.1
	PEMT	NM_001267552.2		c.204+10915G>C		intron	N/A	NP_001254481.1
	PEMT	NM_001267551.2		c.138+10915G>C		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+10915G>C		intron	N/A	ENSP00000255389.5
	PEMT	ENST00000395782.5	TSL:1	c.93+10915G>C		intron	N/A	ENSP00000379128.1
	PEMT	ENST00000395783.5	TSL:1	c.93+10915G>C		intron	N/A	ENSP00000379129.1

Frequencies

GnomAD3 genomes AF: 0.0657 AC: 9997 AN: 152156 Hom.: 850 Cov.: 33

Gnomad AFR AF: 0.193

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0382

Gnomad ASJ AF: 0.0340

Gnomad EAS AF: 0.103

Gnomad SAS AF: 0.0349

Gnomad FIN AF: 0.00207

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.00623

Gnomad OTH AF: 0.0688

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

GnomAD4 genome AF: 0.0660 AC: 10045 AN: 152274 Hom.: 857 Cov.: 33 AF XY: 0.0651 AC XY: 4851 AN XY: 74460

African (AFR) AF: 0.193 AC: 8026 AN: 41524

American (AMR) AF: 0.0380 AC: 581 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0340 AC: 118 AN: 3472

East Asian (EAS) AF: 0.103 AC: 533 AN: 5180

South Asian (SAS) AF: 0.0360 AC: 174 AN: 4832

European-Finnish (FIN) AF: 0.00207 AC: 22 AN: 10616

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.00623 AC: 424 AN: 68034

Other (OTH) AF: 0.0686 AC: 145 AN: 2114

Alfa AF: 0.00410 Hom.: 2

Bravo AF: 0.0755

Asia WGS AF: 0.0690 AC: 241 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.067
DANN	Benign	0.78
PhyloP100		-3.1
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: rs4646361; hg19: chr17-17469319;