rs2941504

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_033419.5(PGAP3):c.465T>C(p.Val155Val) 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

Publications

63 publications found

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 Gene-Disease associations (from GenCC):

hyperphosphatasia with intellectual disability syndrome 4
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, ClinGen, Labcorp Genetics (formerly Invitae)
hyperphosphatasia-intellectual disability syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

PGAP3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
PGAP3	NM_033419.5 link	c.465T>C	p.Val155Val	synonymous_variant	Exon 4 of 8	ENST00000300658.9	NP_219487.3	Q96FM1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PGAP3	ENST00000300658.9 link	c.465T>C	p.Val155Val	synonymous_variant	Exon 4 of 8	1	NM_033419.5	ENSP00000300658.4		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

GnomAD2 exomes

AF:

0.668

AC:

103951

AN:

155724

AF XY:

0.680

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 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

African (AFR)

AF:

0.546

AC:

17230

AN:

31548

American (AMR)

AF:

0.604

AC:

21527

AN:

35636

Ashkenazi Jewish (ASJ)

AF:

0.708

AC:

17791

AN:

25138

East Asian (EAS)

AF:

0.461

AC:

16519

AN:

35828

South Asian (SAS)

AF:

0.771

AC:

60987

AN:

79122

European-Finnish (FIN)

AF:

0.720

AC:

35350

AN:

49118

Middle Eastern (MID)

AF:

0.772

AC:

4391

AN:

5690

European-Non Finnish (NFE)

AF:

0.699

AC:

752816

AN:

1077740

Other (OTH)

AF:

0.681

AC:

39462

AN:

57936

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.456

Heterozygous variant carriers

15109

30218

45328

60437

75546

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19258

38516

57774

77032

96290

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.637

AC:

96860

AN:

151990

Hom.:

31413

Cov.:

AF XY:

0.636

AC XY:

47261

AN XY:

74288

show subpopulations

African (AFR)

AF:

0.550

AC:

22782

AN:

41452

American (AMR)

AF:

0.593

AC:

9052

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.700

AC:

2428

AN:

3470

East Asian (EAS)

AF:

0.410

AC:

2112

AN:

5156

South Asian (SAS)

AF:

0.737

AC:

3554

AN:

4824

European-Finnish (FIN)

AF:

0.720

AC:

7619

AN:

10576

Middle Eastern (MID)

AF:

0.684

AC:

201

AN:

294

European-Non Finnish (NFE)

AF:

0.693

AC:

47041

AN:

67922

Other (OTH)

AF:

0.630

AC:

1331

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1793

3587

5380

7174

8967

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

788

1576

2364

3152

3940

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.684

Hom.:

66969

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

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jun 14, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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. -

Hyperphosphatasia with intellectual disability syndrome 4

Benign:1

Sep 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

9.9

(source)

DANN

Benign

0.75

PhyloP100

0.069

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over