rs1565922

Positions:

• chr17-39674782-A-G
• chr17-39674782-A-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_033419.5(PGAP3):​c.433-103T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.673 in 1,156,540 control chromosomes in the GnomAD database, including 265,722 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.62 (30239 hom., cov: 30)
  • Exomes 𝑓: 0.68 (235483 hom.)
• Consequence: PGAP3 NM_033419.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.397

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]

PGAP3 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 17-39674782-A-G is Benign according to our data. Variant chr17-39674782-A-G is described in ClinVar as [Benign]. Clinvar id is 1282412.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.715 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PGAP3	NM_033419.5	c.433-103T>C		intron_variant		ENST00000300658.9	NP_219487.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PGAP3	ENST00000300658.9	c.433-103T>C		intron_variant		1	NM_033419.5	ENSP00000300658.4

Frequencies

GnomAD3 genomes AF: 0.623 AC: 94450 AN: 151680 Hom.: 30210 Cov.: 30

Gnomad AFR AF: 0.501

Gnomad AMI AF: 0.815

Gnomad AMR AF: 0.583

Gnomad ASJ AF: 0.699

Gnomad EAS AF: 0.409

Gnomad SAS AF: 0.734

Gnomad FIN AF: 0.721

Gnomad MID AF: 0.688

Gnomad NFE AF: 0.692

Gnomad OTH AF: 0.619

GnomAD4 exome AF: 0.681 AC: 684043 AN: 1004742 Hom.: 235483 AF XY: 0.685 AC XY: 346719 AN XY: 506310

Gnomad4 AFR exome AF: 0.495

Gnomad4 AMR exome AF: 0.584

Gnomad4 ASJ exome AF: 0.700

Gnomad4 EAS exome AF: 0.462

Gnomad4 SAS exome AF: 0.762

Gnomad4 FIN exome AF: 0.714

Gnomad4 NFE exome AF: 0.691

Gnomad4 OTH exome AF: 0.670

GnomAD4 genome AF: 0.623 AC: 94534 AN: 151798 Hom.: 30239 Cov.: 30 AF XY: 0.622 AC XY: 46140 AN XY: 74192

Gnomad4 AFR AF: 0.501

Gnomad4 AMR AF: 0.583

Gnomad4 ASJ AF: 0.699

Gnomad4 EAS AF: 0.409

Gnomad4 SAS AF: 0.736

Gnomad4 FIN AF: 0.721

Gnomad4 NFE AF: 0.692

Gnomad4 OTH AF: 0.620

Alfa AF: 0.682 Hom.: 44777

Bravo AF: 0.603

Asia WGS AF: 0.631 AC: 2194 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 27, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.39
DANN	Benign	0.53

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: rs1565922; hg19: chr17-37831035; COSMIC: COSV54092915; COSMIC: COSV54092915;