NM_148172.3:c.205-14084G>A

Variant names:

• chr17-17536479-C-T
• rs936108
• NM_148172.3:c.205-14084G>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.205-14084G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.456 in 152,086 control chromosomes in the GnomAD database, including 16,403 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 (16403 hom., cov: 33)
• Consequence: PEMT NM_148172.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.538
• Publications: 7 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=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.53 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.205-14084G>A		intron	N/A	NP_680477.1	Q9UBM1-2
	PEMT	NM_001267552.2		c.205-14084G>A		intron	N/A	NP_001254481.1	Q9UBM1-3
	PEMT	NM_001267551.2		c.139-14084G>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.205-14084G>A		intron	N/A	ENSP00000255389.5	Q9UBM1-2
	PEMT	ENST00000395782.5	TSL:1	c.94-14084G>A		intron	N/A	ENSP00000379128.1	Q9UBM1-1
	PEMT	ENST00000395783.5	TSL:1	c.94-14084G>A		intron	N/A	ENSP00000379129.1	Q9UBM1-1

Frequencies

GnomAD3 genomes AF: 0.456 AC: 69242 AN: 151968 Hom.: 16399 Cov.: 33

Gnomad AFR AF: 0.341

Gnomad AMI AF: 0.516

Gnomad AMR AF: 0.473

Gnomad ASJ AF: 0.501

Gnomad EAS AF: 0.312

Gnomad SAS AF: 0.326

Gnomad FIN AF: 0.479

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.534

Gnomad OTH AF: 0.454

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

GnomAD4 genome AF: 0.456 AC: 69277 AN: 152086 Hom.: 16403 Cov.: 33 AF XY: 0.450 AC XY: 33444 AN XY: 74318

African (AFR) AF: 0.341 AC: 14147 AN: 41472

American (AMR) AF: 0.473 AC: 7232 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.501 AC: 1737 AN: 3470

East Asian (EAS) AF: 0.312 AC: 1608 AN: 5162

South Asian (SAS) AF: 0.326 AC: 1570 AN: 4818

European-Finnish (FIN) AF: 0.479 AC: 5075 AN: 10584

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

European-Non Finnish (NFE) AF: 0.534 AC: 36333 AN: 67984

Other (OTH) AF: 0.454 AC: 956 AN: 2108

Alfa AF: 0.490 Hom.: 2454

Bravo AF: 0.451

Asia WGS AF: 0.313 AC: 1088 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.096
DANN	Benign	0.53
PhyloP100		-0.54
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: rs936108; hg19: chr17-17439793;