rs12150298

Positions:

• chr17-39678288-T-C
• chr17-39678288-T-G

Variant summary

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

The ENST00000300658.9(PGAP3):​c.433-3609A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.584 in 152,020 control chromosomes in the GnomAD database, including 26,903 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 0.58 (26903 hom., cov: 32)
• Consequence: PGAP3 ENST00000300658.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.04

Genes affected

PGAP3 (HGNC:23719): (post-GPI attachment to proteins phospholipase 3) This gene encodes a glycosylphosphatidylinositol (GPI)-specific phospholipase that primarily localizes to the Golgi apparatus. This ubiquitously expressed gene is predicted to encode a seven-transmembrane protein that removes unsaturated fatty acids from the sn-2 position of GPI. The remodeling of the constituent fatty acids on GPI is thought to be important for the proper association between GPI-anchored proteins and lipid rafts. The tethering of proteins to plasma membranes via posttranslational GPI-anchoring is thought to play a role in protein sorting and trafficking. Mutations in this gene cause an autosomal recessive form of neurologic hyperphosphatasia with cognitive disability (HPMRS4). Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Jul 2017]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.677 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PGAP3	NM_033419.5	c.433-3609A>G		intron_variant		ENST00000300658.9	NP_219487.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PGAP3	ENST00000300658.9	c.433-3609A>G		intron_variant		1	NM_033419.5	ENSP00000300658	P1

Frequencies

GnomAD3 genomes AF: 0.584 AC: 88680 AN: 151902 Hom.: 26872 Cov.: 32

Gnomad AFR AF: 0.437

Gnomad AMI AF: 0.741

Gnomad AMR AF: 0.560

Gnomad ASJ AF: 0.676

Gnomad EAS AF: 0.407

Gnomad SAS AF: 0.696

Gnomad FIN AF: 0.692

Gnomad MID AF: 0.658

Gnomad NFE AF: 0.660

Gnomad OTH AF: 0.584

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

GnomAD4 genome AF: 0.584 AC: 88759 AN: 152020 Hom.: 26903 Cov.: 32 AF XY: 0.583 AC XY: 43345 AN XY: 74302

Gnomad4 AFR AF: 0.438

Gnomad4 AMR AF: 0.560

Gnomad4 ASJ AF: 0.676

Gnomad4 EAS AF: 0.407

Gnomad4 SAS AF: 0.697

Gnomad4 FIN AF: 0.692

Gnomad4 NFE AF: 0.660

Gnomad4 OTH AF: 0.586

Alfa AF: 0.646 Hom.: 15377

Bravo AF: 0.565

Asia WGS AF: 0.600 AC: 2087 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.21
DANN	Benign	0.47

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: rs12150298; hg19: chr17-37834541;