NM_148172.3:c.320+3240G>A

Variant names:

• chr17-17519040-C-T
• rs1108579
• NM_148172.3:c.320+3240G>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.320+3240G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.408 in 152,162 control chromosomes in the GnomAD database, including 13,751 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 0.41 (13746 hom., cov: 33)
  • Exomes 𝑓: 0.53 (5 hom.)
• Consequence: PEMT NM_148172.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.736
• 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]

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 = 0.509 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.320+3240G>A		intron	N/A	NP_680477.1
	PEMT	NM_001267552.2		c.320+3240G>A		intron	N/A	NP_001254481.1
	PEMT	NM_001267551.2		c.254+3240G>A		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.320+3240G>A		intron	N/A	ENSP00000255389.5
	PEMT	ENST00000395782.5	TSL:1	c.209+3240G>A		intron	N/A	ENSP00000379128.1
	PEMT	ENST00000395783.5	TSL:1	c.209+3240G>A		intron	N/A	ENSP00000379129.1

Frequencies

GnomAD3 genomes AF: 0.408 AC: 62031 AN: 152004 Hom.: 13751 Cov.: 33

Gnomad AFR AF: 0.286

Gnomad AMI AF: 0.518

Gnomad AMR AF: 0.358

Gnomad ASJ AF: 0.399

Gnomad EAS AF: 0.117

Gnomad SAS AF: 0.230

Gnomad FIN AF: 0.498

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.514

Gnomad OTH AF: 0.404

GnomAD4 exome AF: 0.525 AC: 21 AN: 40 Hom.: 5 Cov.: 0 AF XY: 0.571 AC XY: 16 AN XY: 28

African (AFR) AF: 0.500 AC: 2 AN: 4

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.667 AC: 4 AN: 6

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.500 AC: 13 AN: 26

Other (OTH) AF: 0.500 AC: 2 AN: 4

GnomAD4 genome AF: 0.408 AC: 62042 AN: 152122 Hom.: 13746 Cov.: 33 AF XY: 0.402 AC XY: 29862 AN XY: 74368

African (AFR) AF: 0.285 AC: 11848 AN: 41518

American (AMR) AF: 0.358 AC: 5468 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.399 AC: 1385 AN: 3470

East Asian (EAS) AF: 0.117 AC: 608 AN: 5190

South Asian (SAS) AF: 0.229 AC: 1103 AN: 4826

European-Finnish (FIN) AF: 0.498 AC: 5257 AN: 10556

Middle Eastern (MID) AF: 0.456 AC: 134 AN: 294

European-Non Finnish (NFE) AF: 0.514 AC: 34910 AN: 67964

Other (OTH) AF: 0.406 AC: 857 AN: 2112

Alfa AF: 0.454 Hom.: 8579

Bravo AF: 0.391

Asia WGS AF: 0.235 AC: 816 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	0.18
DANN	Benign	0.39
PhyloP100		-0.74
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: rs1108579; hg19: chr17-17422354;