Variant chr17-39672876-A-G 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.900-10T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.686 in 1,612,766 control chromosomes in the GnomAD database, including 383,224 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.64 ( 31637 hom., cov: 33)

Exomes 𝑓: 0.69 ( 351587 hom. )

Consequence

PGAP3
NM_033419.5 intron

Scores

Splicing: ADA: 0.0002155

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -1.73

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:

PGAP3 (HGNC:):

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=-0.81).

BP6

Variant 17-39672876-A-G is Benign according to our data. Variant chr17-39672876-A-G is described in ClinVar as [Benign]. Clinvar id is 1268616.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.718 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PGAP3	NM_033419.5 linkuse as main transcript	c.900-10T>C		intron_variant		ENST00000300658.9	NP_219487.3	Q96FM1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PGAP3	ENST00000300658.9 linkuse as main transcript	c.900-10T>C		intron_variant		1	NM_033419.5	ENSP00000300658.4		Q96FM1-1

Frequencies

GnomAD3 genomes

AF:

0.639

AC:

97147

AN:

151920

Hom.:

31609

Cov.:

show subpopulations

Gnomad AFR

AF:

0.556

Gnomad AMI

AF:

0.812

Gnomad AMR

AF:

0.592

Gnomad ASJ

AF:

0.699

Gnomad EAS

AF:

0.409

Gnomad SAS

AF:

0.737

Gnomad FIN

AF:

0.721

Gnomad MID

AF:

0.699

Gnomad NFE

AF:

0.693

Gnomad OTH

AF:

0.629

GnomAD3 exomes

AF:

0.666

AC:

166086

AN:

249254

Hom.:

56694

AF XY:

0.678

AC XY:

91474

AN XY:

134836

show subpopulations

Gnomad AFR exome

AF:

0.555

Gnomad AMR exome

AF:

0.610

Gnomad ASJ exome

AF:

0.713

Gnomad EAS exome

AF:

0.379

Gnomad SAS exome

AF:

0.765

Gnomad FIN exome

AF:

0.725

Gnomad NFE exome

AF:

0.703

Gnomad OTH exome

AF:

0.682

GnomAD4 exome

AF:

0.691

AC:

1009671

AN:

1460730

Hom.:

351587

Cov.:

AF XY:

0.694

AC XY:

504628

AN XY:

726714

show subpopulations

Gnomad4 AFR exome

AF:

0.553

Gnomad4 AMR exome

AF:

0.606

Gnomad4 ASJ exome

AF:

0.708

Gnomad4 EAS exome

AF:

0.455

Gnomad4 SAS exome

AF:

0.770

Gnomad4 FIN exome

AF:

0.719

Gnomad4 NFE exome

AF:

0.699

Gnomad4 OTH exome

AF:

0.682

GnomAD4 genome

AF:

0.640

AC:

97237

AN:

152036

Hom.:

31637

Cov.:

AF XY:

0.639

AC XY:

47457

AN XY:

74322

show subpopulations

Gnomad4 AFR

AF:

0.557

Gnomad4 AMR

AF:

0.593

Gnomad4 ASJ

AF:

0.699

Gnomad4 EAS

AF:

0.409

Gnomad4 SAS

AF:

0.738

Gnomad4 FIN

AF:

0.721

Gnomad4 NFE

AF:

0.693

Gnomad4 OTH

AF:

0.631

Alfa

AF:

0.666

Hom.:

12419

Bravo

AF:

0.622

Asia WGS

AF:

0.634

AC:

2205

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 31, 2018	- -

Hyperphosphatasia with intellectual disability syndrome 4

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.27

DANN

Benign

0.71

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00022

dbscSNV1_RF

Benign

0.0080

SpliceAI score (max)

0.080

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