17-17517873-G-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_148172.3(PEMT):​c.320+4407C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000796 in 628,264 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000020 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000042 (0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PEMT	NM_148172.3	c.320+4407C>A		intron_variant	Intron 3 of 6	ENST00000255389.10	NP_680477.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PEMT	ENST00000255389.10	c.320+4407C>A		intron_variant	Intron 3 of 6	1	NM_148172.3	ENSP00000255389.5

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152012 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000420 AC: 2 AN: 476252 Hom.: 0 AF XY: 0.00000446 AC XY: 1 AN XY: 224146

African (AFR) AF: 0.00 AC: 0 AN: 8904

American (AMR) AF: 0.00 AC: 0 AN: 534

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2918

East Asian (EAS) AF: 0.00 AC: 0 AN: 1984

South Asian (SAS) AF: 0.000214 AC: 2 AN: 9340

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 176

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 958

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 435974

Other (OTH) AF: 0.00 AC: 0 AN: 15464

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152012 Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2 AN XY: 74242

African (AFR) AF: 0.00 AC: 0 AN: 41366

American (AMR) AF: 0.00 AC: 0 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10596

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 67972

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.000208 Hom.: 1143

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.032
DANN	Benign	0.076
PhyloP100		-4.4

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;