Variant 11-3797940-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 4P and 4B. PM1PM2BP4_Strong

The ENST00000300730.10(PGAP2):c.97A>T(p.Arg33Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000174 in 1,548,676 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/15 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

PGAP2
ENST00000300730.10 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.870

Variant links:

Genes affected

PGAP2 (HGNC:17893): (post-GPI attachment to proteins 2) The protein encoded by this gene plays a role in the maturation of glycosylphosphatidylinositol (GPI) anchors on GPI-anchored proteins. Mutations in this gene are associated with an autosomal recessive syndrome characterized by hyperphosphatasia and intellectual disability. [provided by RefSeq, Jul 2017]

PGAP2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM1

In a chain Post-GPI attachment to proteins factor 2 (size 253) in uniprot entity PGAP2_HUMAN there are 29 pathogenic changes around while only 8 benign (78%) in ENST00000300730.10

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.05198297).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons
PGAP2	NM_001256236.1 linkuse as main transcript	c.97A>T	p.Arg33Trp	missense_variant	1/8
PGAP2	NM_001283038.1 linkuse as main transcript	c.97A>T	p.Arg33Trp	missense_variant	1/7
PGAP2	NM_001145438.2 linkuse as main transcript	c.97A>T	p.Arg33Trp	missense_variant	1/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	UniProt
PGAP2	ENST00000300730.10 linkuse as main transcript	c.97A>T	p.Arg33Trp	missense_variant	1/7	1	Q9UHJ9-5
PGAP2	ENST00000396993.8 linkuse as main transcript	c.-368A>T		5_prime_UTR_variant	1/6	1
PGAP2	ENST00000465237.6 linkuse as main transcript	n.33A>T		non_coding_transcript_exon_variant	1/3	1

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000771

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000463

AC:

AN:

151080

Hom.:

AF XY:

0.0000498

AC XY:

AN XY:

80340

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000681

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000165

AC:

AN:

1396358

Hom.:

Cov.:

AF XY:

0.0000232

AC XY:

AN XY:

688706

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000598

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.28e-7

Gnomad4 OTH exome

AF:

0.0000173

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152318

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74498

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000773

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000189

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 29, 2023

The c.97A>T (p.R33W) alteration is located in exon 1 (coding exon 1) of the PGAP2 gene. This alteration results from a A to T substitution at nucleotide position 97, causing the arginine (R) at amino acid position 33 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Uncertain

1.0

Eigen

Benign

-0.36

Eigen_PC

Benign

-0.31

FATHMM_MKL

Benign

0.27

LIST_S2

Benign

0.60

T;T

M_CAP

Benign

0.0073

MetaRNN

Benign

0.052

T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

0.86

D;D;N;N

PrimateAI

Benign

0.41

PROVEAN

Benign

0.35

N;N

REVEL

Benign

0.047

Sift

Pathogenic

0.0

D;D

Polyphen

0.76

P;.

Vest4

0.23

MutPred

0.30

Loss of disorder (P = 0.0155);Loss of disorder (P = 0.0155);

MVP

0.41

ClinPred

0.16

GERP RS

3.0

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