Variant chr17-39673351-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_033419.5(PGAP3):c.695-96G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.654 in 1,555,400 control chromosomes in the GnomAD database, including 341,215 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.54 ( 24877 hom., cov: 32)

Exomes 𝑓: 0.67 ( 316338 hom. )

Consequence

PGAP3
NM_033419.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.430

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.67).

BP6

Variant 17-39673351-C-T is Benign according to our data. Variant chr17-39673351-C-T is described in ClinVar as [Benign]. Clinvar id is 1277582.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.678 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PGAP3	NM_033419.5 linkuse as main transcript	c.695-96G>A		intron_variant		ENST00000300658.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PGAP3	ENST00000300658.9 linkuse as main transcript	c.695-96G>A		intron_variant		1	NM_033419.5	P1	Q96FM1-1

Frequencies

GnomAD3 genomes

AF:

0.541

AC:

82245

AN:

151908

Hom.:

24862

Cov.:

show subpopulations

Gnomad AFR

AF:

0.268

Gnomad AMI

AF:

0.791

Gnomad AMR

AF:

0.546

Gnomad ASJ

AF:

0.679

Gnomad EAS

AF:

0.407

Gnomad SAS

AF:

0.697

Gnomad FIN

AF:

0.695

Gnomad MID

AF:

0.652

Gnomad NFE

AF:

0.671

Gnomad OTH

AF:

0.559

GnomAD4 exome

AF:

0.666

AC:

935196

AN:

1403374

Hom.:

316338

Cov.:

AF XY:

0.670

AC XY:

466041

AN XY:

695846

show subpopulations

Gnomad4 AFR exome

AF:

0.265

Gnomad4 AMR exome

AF:

0.583

Gnomad4 ASJ exome

AF:

0.688

Gnomad4 EAS exome

AF:

0.456

Gnomad4 SAS exome

AF:

0.735

Gnomad4 FIN exome

AF:

0.692

Gnomad4 NFE exome

AF:

0.683

Gnomad4 OTH exome

AF:

0.645

GnomAD4 genome

AF:

0.541

AC:

82296

AN:

152026

Hom.:

24877

Cov.:

AF XY:

0.542

AC XY:

40287

AN XY:

74302

show subpopulations

Gnomad4 AFR

AF:

0.268

Gnomad4 AMR

AF:

0.546

Gnomad4 ASJ

AF:

0.679

Gnomad4 EAS

AF:

0.407

Gnomad4 SAS

AF:

0.698

Gnomad4 FIN

AF:

0.695

Gnomad4 NFE

AF:

0.671

Gnomad4 OTH

AF:

0.562

Alfa

AF:

0.645

Hom.:

31259

Bravo

AF:

0.515

Asia WGS

AF:

0.595

AC:

2068

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

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

-0.67

CADD

Benign

8.9

DANN

Benign

0.79

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over