Variant rs2941504 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_033419.5(PGAP3):c.465T>C(p.Val155=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.686 in 1,549,746 control chromosomes in the GnomAD database, including 367,720 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.64 ( 31413 hom., cov: 32)

Exomes 𝑓: 0.69 ( 336307 hom. )

Consequence

PGAP3
NM_033419.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.0690

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.66).

BP6

Variant 17-39674647-A-G is Benign according to our data. Variant chr17-39674647-A-G is described in ClinVar as [Benign]. Clinvar id is 679984.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.069 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.717 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.465T>C	p.Val155=	synonymous_variant	4/8	ENST00000300658.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PGAP3	ENST00000300658.9 linkuse as main transcript	c.465T>C	p.Val155=	synonymous_variant	4/8	1	NM_033419.5	P1	Q96FM1-1

Frequencies

GnomAD3 genomes

AF:

0.637

AC:

96769

AN:

151872

Hom.:

31384

Cov.:

show subpopulations

Gnomad AFR

AF:

0.549

Gnomad AMI

AF:

0.813

Gnomad AMR

AF:

0.592

Gnomad ASJ

AF:

0.700

Gnomad EAS

AF:

0.409

Gnomad SAS

AF:

0.736

Gnomad FIN

AF:

0.720

Gnomad MID

AF:

0.699

Gnomad NFE

AF:

0.693

Gnomad OTH

AF:

0.629

GnomAD3 exomes

AF:

0.668

AC:

103951

AN:

155724

Hom.:

35682

AF XY:

0.680

AC XY:

55720

AN XY:

81888

show subpopulations

Gnomad AFR exome

AF:

0.543

Gnomad AMR exome

AF:

0.610

Gnomad ASJ exome

AF:

0.714

Gnomad EAS exome

AF:

0.377

Gnomad SAS exome

AF:

0.770

Gnomad FIN exome

AF:

0.728

Gnomad NFE exome

AF:

0.702

Gnomad OTH exome

AF:

0.684

GnomAD4 exome

AF:

0.691

AC:

966073

AN:

1397756

Hom.:

336307

Cov.:

AF XY:

0.694

AC XY:

478541

AN XY:

689434

show subpopulations

Gnomad4 AFR exome

AF:

0.546

Gnomad4 AMR exome

AF:

0.604

Gnomad4 ASJ exome

AF:

0.708

Gnomad4 EAS exome

AF:

0.461

Gnomad4 SAS exome

AF:

0.771

Gnomad4 FIN exome

AF:

0.720

Gnomad4 NFE exome

AF:

0.699

Gnomad4 OTH exome

AF:

0.681

GnomAD4 genome

AF:

0.637

AC:

96860

AN:

151990

Hom.:

31413

Cov.:

AF XY:

0.636

AC XY:

47261

AN XY:

74288

show subpopulations

Gnomad4 AFR

AF:

0.550

Gnomad4 AMR

AF:

0.593

Gnomad4 ASJ

AF:

0.700

Gnomad4 EAS

AF:

0.410

Gnomad4 SAS

AF:

0.737

Gnomad4 FIN

AF:

0.720

Gnomad4 NFE

AF:

0.693

Gnomad4 OTH

AF:

0.630

Alfa

AF:

0.689

Hom.:

55040

Bravo

AF:

0.620

Asia WGS

AF:

0.634

AC:

2206

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	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 14, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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

-0.66

CADD

Benign

9.9

DANN

Benign

0.75

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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