17-17529430-G-A

Variant names:

• chr17-17529430-G-A
• rs4646396
• NM_148172.3:c.205-7035C>T

Variant summary

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

The NM_148172.3(PEMT):​c.205-7035C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.462 in 152,080 control chromosomes in the GnomAD database, including 16,856 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 0.46 (16856 hom., cov: 33)
• Consequence: PEMT NM_148172.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.354
• Publications: 5 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 (NFE) allele frequency at 95% confidence interval = 0.536 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.205-7035C>T		intron	N/A	NP_680477.1
	PEMT	NM_001267552.2		c.205-7035C>T		intron	N/A	NP_001254481.1
	PEMT	NM_001267551.2		c.139-7035C>T		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.205-7035C>T		intron	N/A	ENSP00000255389.5
	PEMT	ENST00000395782.5	TSL:1	c.94-7035C>T		intron	N/A	ENSP00000379128.1
	PEMT	ENST00000395783.5	TSL:1	c.94-7035C>T		intron	N/A	ENSP00000379129.1

Frequencies

GnomAD3 genomes AF: 0.462 AC: 70188 AN: 151962 Hom.: 16853 Cov.: 33

Gnomad AFR AF: 0.342

Gnomad AMI AF: 0.520

Gnomad AMR AF: 0.476

Gnomad ASJ AF: 0.498

Gnomad EAS AF: 0.312

Gnomad SAS AF: 0.331

Gnomad FIN AF: 0.518

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.541

Gnomad OTH AF: 0.463

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

GnomAD4 genome AF: 0.462 AC: 70218 AN: 152080 Hom.: 16856 Cov.: 33 AF XY: 0.457 AC XY: 33998 AN XY: 74364

African (AFR) AF: 0.342 AC: 14177 AN: 41492

American (AMR) AF: 0.476 AC: 7280 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.498 AC: 1728 AN: 3472

East Asian (EAS) AF: 0.312 AC: 1612 AN: 5170

South Asian (SAS) AF: 0.331 AC: 1592 AN: 4814

European-Finnish (FIN) AF: 0.518 AC: 5487 AN: 10590

Middle Eastern (MID) AF: 0.507 AC: 149 AN: 294

European-Non Finnish (NFE) AF: 0.541 AC: 36744 AN: 67938

Other (OTH) AF: 0.463 AC: 978 AN: 2114

Alfa AF: 0.491 Hom.: 8333

Bravo AF: 0.454

Asia WGS AF: 0.314 AC: 1091 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	0.37
DANN	Benign	0.34
PhyloP100		-0.35
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: rs4646396; hg19: chr17-17432744;