rs1476278

Positions:

• chr17-39679990-C-T

Variant summary

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

The NM_033419.5(PGAP3):​c.432+4607G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.547 in 151,988 control chromosomes in the GnomAD database, including 24,800 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 0.55 (24800 hom., cov: 31)
• Consequence: PGAP3 NM_033419.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.27

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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.676 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PGAP3	NM_033419.5	c.432+4607G>A		intron_variant		ENST00000300658.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PGAP3	ENST00000300658.9	c.432+4607G>A		intron_variant		1	NM_033419.5	P1

Frequencies

GnomAD3 genomes AF: 0.547 AC: 83088 AN: 151870 Hom.: 24780 Cov.: 31

Gnomad AFR AF: 0.312

Gnomad AMI AF: 0.742

Gnomad AMR AF: 0.543

Gnomad ASJ AF: 0.675

Gnomad EAS AF: 0.406

Gnomad SAS AF: 0.695

Gnomad FIN AF: 0.691

Gnomad MID AF: 0.656

Gnomad NFE AF: 0.659

Gnomad OTH AF: 0.562

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

GnomAD4 genome AF: 0.547 AC: 83148 AN: 151988 Hom.: 24800 Cov.: 31 AF XY: 0.548 AC XY: 40696 AN XY: 74270

Gnomad4 AFR AF: 0.312

Gnomad4 AMR AF: 0.544

Gnomad4 ASJ AF: 0.675

Gnomad4 EAS AF: 0.406

Gnomad4 SAS AF: 0.696

Gnomad4 FIN AF: 0.691

Gnomad4 NFE AF: 0.659

Gnomad4 OTH AF: 0.563

Alfa AF: 0.560 Hom.: 5332

Bravo AF: 0.522

Asia WGS AF: 0.581 AC: 2019 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.19
DANN	Benign	0.64

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: rs1476278; hg19: chr17-37836243;