17-17517873-G-C

Variant names:

• chr17-17517873-G-C
• rs4646402
• NM_148172.3:c.320+4407C>G

Variant summary

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

The NM_148172.3(PEMT):​c.320+4407C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.568 in 626,550 control chromosomes in the GnomAD database, including 102,477 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 0.52 (20955 hom., cov: 33)
  • Exomes 𝑓: 0.58 (81522 hom.)
• Consequence: PEMT NM_148172.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.45
• Publications: 2 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=-1.01).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.578 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.320+4407C>G		intron	N/A	NP_680477.1	Q9UBM1-2
	PEMT	NM_001267552.2		c.320+4407C>G		intron	N/A	NP_001254481.1	Q9UBM1-3
	PEMT	NM_001267551.2		c.254+4407C>G		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.320+4407C>G		intron	N/A	ENSP00000255389.5	Q9UBM1-2
	PEMT	ENST00000395782.5	TSL:1	c.209+4407C>G		intron	N/A	ENSP00000379128.1	Q9UBM1-1
	PEMT	ENST00000395783.5	TSL:1	c.209+4407C>G		intron	N/A	ENSP00000379129.1	Q9UBM1-1

Frequencies

GnomAD3 genomes AF: 0.518 AC: 78652 AN: 151956 Hom.: 20956 Cov.: 33

Gnomad AFR AF: 0.464

Gnomad AMI AF: 0.554

Gnomad AMR AF: 0.448

Gnomad ASJ AF: 0.550

Gnomad EAS AF: 0.301

Gnomad SAS AF: 0.368

Gnomad FIN AF: 0.569

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.583

Gnomad OTH AF: 0.520

GnomAD4 exome AF: 0.584 AC: 277104 AN: 474476 Hom.: 81522 AF XY: 0.584 AC XY: 130442 AN XY: 223370

African (AFR) AF: 0.453 AC: 4021 AN: 8872

American (AMR) AF: 0.436 AC: 233 AN: 534

Ashkenazi Jewish (ASJ) AF: 0.548 AC: 1592 AN: 2906

East Asian (EAS) AF: 0.290 AC: 572 AN: 1974

South Asian (SAS) AF: 0.388 AC: 3612 AN: 9308

European-Finnish (FIN) AF: 0.574 AC: 101 AN: 176

Middle Eastern (MID) AF: 0.506 AC: 483 AN: 954

European-Non Finnish (NFE) AF: 0.594 AC: 258042 AN: 434344

Other (OTH) AF: 0.548 AC: 8448 AN: 15408

GnomAD4 genome AF: 0.517 AC: 78683 AN: 152074 Hom.: 20955 Cov.: 33 AF XY: 0.511 AC XY: 38007 AN XY: 74338

African (AFR) AF: 0.463 AC: 19197 AN: 41468

American (AMR) AF: 0.448 AC: 6844 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.550 AC: 1907 AN: 3470

East Asian (EAS) AF: 0.301 AC: 1559 AN: 5174

South Asian (SAS) AF: 0.367 AC: 1769 AN: 4816

European-Finnish (FIN) AF: 0.569 AC: 6032 AN: 10594

Middle Eastern (MID) AF: 0.537 AC: 158 AN: 294

European-Non Finnish (NFE) AF: 0.583 AC: 39606 AN: 67946

Other (OTH) AF: 0.523 AC: 1106 AN: 2114

Alfa AF: 0.418 Hom.: 1143

Bravo AF: 0.504

Asia WGS AF: 0.369 AC: 1285 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.033
DANN	Benign	0.23
PhyloP100		-4.4
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: rs4646402; hg19: chr17-17421187; COSMIC: COSV55133286;