rs4646342

Variant names:

• chr17-17589958-G-A
• rs4646342
• NM_148172.3:c.96+1573C>T

Your query was ambiguous. Multiple possible variants found:

• chr17-17589958-G-A
• chr17-17589958-G-C

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+1573C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.423 in 151,830 control chromosomes in the GnomAD database, including 13,772 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 0.42 (13772 hom., cov: 30)
• Consequence: PEMT NM_148172.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.212
• Publications: 9 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.469 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+1573C>T		intron	N/A	NP_680477.1	Q9UBM1-2
	PEMT	NM_001267552.2		c.96+1573C>T		intron	N/A	NP_001254481.1	Q9UBM1-3
	PEMT	NM_001267551.2		c.30+1639C>T		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+1573C>T		intron	N/A	ENSP00000255389.5	Q9UBM1-2
	PEMT	ENST00000900344.1		c.96+1573C>T		intron	N/A	ENSP00000570403.1
	PEMT	ENST00000900343.1		c.96+1573C>T		intron	N/A	ENSP00000570402.1

Frequencies

GnomAD3 genomes AF: 0.423 AC: 64099 AN: 151712 Hom.: 13755 Cov.: 30

Gnomad AFR AF: 0.474

Gnomad AMI AF: 0.417

Gnomad AMR AF: 0.363

Gnomad ASJ AF: 0.429

Gnomad EAS AF: 0.307

Gnomad SAS AF: 0.229

Gnomad FIN AF: 0.349

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.437

Gnomad OTH AF: 0.423

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

GnomAD4 genome AF: 0.423 AC: 64158 AN: 151830 Hom.: 13772 Cov.: 30 AF XY: 0.413 AC XY: 30662 AN XY: 74180

African (AFR) AF: 0.475 AC: 19634 AN: 41352

American (AMR) AF: 0.363 AC: 5539 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.429 AC: 1488 AN: 3472

East Asian (EAS) AF: 0.308 AC: 1582 AN: 5144

South Asian (SAS) AF: 0.230 AC: 1103 AN: 4800

European-Finnish (FIN) AF: 0.349 AC: 3681 AN: 10542

Middle Eastern (MID) AF: 0.500 AC: 146 AN: 292

European-Non Finnish (NFE) AF: 0.437 AC: 29718 AN: 67932

Other (OTH) AF: 0.420 AC: 888 AN: 2112

Alfa AF: 0.398 Hom.: 5768

Bravo AF: 0.429

Asia WGS AF: 0.300 AC: 1043 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.2
DANN	Benign	0.43
PhyloP100		0.21
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: rs4646342; hg19: chr17-17493272;