NM_148172.3:c.96+2768C>A

Variant names:

• chr17-17588763-G-T
• rs4646343
• NM_148172.3:c.96+2768C>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.96+2768C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.331 in 152,090 control chromosomes in the GnomAD database, including 9,837 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 0.33 (9837 hom., cov: 33)
• Consequence: PEMT NM_148172.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.63
• Publications: 16 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=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.448 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.96+2768C>A		intron	N/A	NP_680477.1	Q9UBM1-2
	PEMT	NM_001267552.2		c.96+2768C>A		intron	N/A	NP_001254481.1	Q9UBM1-3
	PEMT	NM_001267551.2		c.30+2834C>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.96+2768C>A		intron	N/A	ENSP00000255389.5	Q9UBM1-2
	PEMT	ENST00000900344.1		c.96+2768C>A		intron	N/A	ENSP00000570403.1
	PEMT	ENST00000900343.1		c.96+2768C>A		intron	N/A	ENSP00000570402.1

Frequencies

GnomAD3 genomes AF: 0.331 AC: 50319 AN: 151972 Hom.: 9838 Cov.: 33

Gnomad AFR AF: 0.137

Gnomad AMI AF: 0.416

Gnomad AMR AF: 0.369

Gnomad ASJ AF: 0.400

Gnomad EAS AF: 0.0994

Gnomad SAS AF: 0.214

Gnomad FIN AF: 0.385

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.453

Gnomad OTH AF: 0.342

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

GnomAD4 genome AF: 0.331 AC: 50334 AN: 152090 Hom.: 9837 Cov.: 33 AF XY: 0.325 AC XY: 24184 AN XY: 74340

African (AFR) AF: 0.137 AC: 5679 AN: 41500

American (AMR) AF: 0.369 AC: 5654 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.400 AC: 1387 AN: 3470

East Asian (EAS) AF: 0.0997 AC: 514 AN: 5158

South Asian (SAS) AF: 0.214 AC: 1034 AN: 4826

European-Finnish (FIN) AF: 0.385 AC: 4066 AN: 10562

Middle Eastern (MID) AF: 0.469 AC: 138 AN: 294

European-Non Finnish (NFE) AF: 0.453 AC: 30766 AN: 67956

Other (OTH) AF: 0.340 AC: 717 AN: 2110

Alfa AF: 0.174 Hom.: 421

Bravo AF: 0.323

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.12
DANN	Benign	0.82
PhyloP100		-1.6
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs4646343; hg19: chr17-17492077;