chr17-17569299-T-C

Position:

• chr17-17569299-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_148172.3(PEMT):​c.204+7621A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.629 in 152,044 control chromosomes in the GnomAD database, including 31,124 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 0.63 (31124 hom., cov: 32)
• Consequence: PEMT NM_148172.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.180

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.792 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PEMT	NM_148172.3	c.204+7621A>G		intron_variant		ENST00000255389.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PEMT	ENST00000255389.10	c.204+7621A>G		intron_variant		1	NM_148172.3

Frequencies

GnomAD3 genomes AF: 0.629 AC: 95599 AN: 151926 Hom.: 31084 Cov.: 32

Gnomad AFR AF: 0.799

Gnomad AMI AF: 0.529

Gnomad AMR AF: 0.571

Gnomad ASJ AF: 0.600

Gnomad EAS AF: 0.416

Gnomad SAS AF: 0.389

Gnomad FIN AF: 0.557

Gnomad MID AF: 0.668

Gnomad NFE AF: 0.587

Gnomad OTH AF: 0.620

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

GnomAD4 genome AF: 0.629 AC: 95705 AN: 152044 Hom.: 31124 Cov.: 32 AF XY: 0.621 AC XY: 46150 AN XY: 74314

Gnomad4 AFR AF: 0.799

Gnomad4 AMR AF: 0.571

Gnomad4 ASJ AF: 0.600

Gnomad4 EAS AF: 0.416

Gnomad4 SAS AF: 0.388

Gnomad4 FIN AF: 0.557

Gnomad4 NFE AF: 0.587

Gnomad4 OTH AF: 0.622

Alfa AF: 0.586 Hom.: 12390

Bravo AF: 0.640

Asia WGS AF: 0.448 AC: 1562 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.2
DANN	Benign	0.37

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

Publications

LitVar

Other links and lift over

dbSNP: rs4244598; hg19: chr17-17472613; COSMIC: COSV55133670;