Variant 11-3808299-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 2P and 14B. PM1BP4_StrongBP6_ModerateBS1BS2

The ENST00000300730.10(PGAP2):c.145T>C(p.Trp49Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000741 in 1,551,456 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. 9/14 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0039 ( 3 hom., cov: 32)

Exomes 𝑓: 0.00039 ( 5 hom. )

Consequence

PGAP2
ENST00000300730.10 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.66

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 Benign. Variant got -12 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

BP4

Computational evidence support a benign effect (MetaRNN=0.0045338273).

BP6

Variant 11-3808299-T-C is Benign according to our data. Variant chr11-3808299-T-C is described in ClinVar as [Benign]. Clinvar id is 2641519.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00394 (600/152196) while in subpopulation AFR AF= 0.0137 (567/41536). AF 95% confidence interval is 0.0127. There are 3 homozygotes in gnomad4. There are 296 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons
PGAP2	NM_001256236.1 linkuse as main transcript	c.145T>C	p.Trp49Arg	missense_variant	2/8
PGAP2	NM_001283038.1 linkuse as main transcript	c.145T>C	p.Trp49Arg	missense_variant	2/7
PGAP2	NM_001145438.2 linkuse as main transcript	c.145T>C	p.Trp49Arg	missense_variant	2/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	UniProt
PGAP2	ENST00000300730.10 linkuse as main transcript	c.145T>C	p.Trp49Arg	missense_variant	2/7	1	Q9UHJ9-5
PGAP2	ENST00000396993.8 linkuse as main transcript	c.-320T>C		5_prime_UTR_variant	2/6	1
PGAP2	ENST00000465237.6 linkuse as main transcript	n.81T>C		non_coding_transcript_exon_variant	2/3	1

Frequencies

GnomAD3 genomes

AF:

0.00394

AC:

599

AN:

152078

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0137

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00124

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00430

GnomAD3 exomes

AF:

0.000799

AC:

125

AN:

156390

Hom.:

AF XY:

0.000543

AC XY:

AN XY:

82934

show subpopulations

Gnomad AFR exome

AF:

0.0143

Gnomad AMR exome

AF:

0.000486

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

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:

0.000392

AC:

549

AN:

1399260

Hom.:

Cov.:

AF XY:

0.000317

AC XY:

219

AN XY:

690126

show subpopulations

Gnomad4 AFR exome

AF:

0.0143

Gnomad4 AMR exome

AF:

0.000644

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000280

Gnomad4 SAS exome

AF:

0.0000252

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000213

Gnomad4 OTH exome

AF:

0.000741

GnomAD4 genome

AF:

0.00394

AC:

600

AN:

152196

Hom.:

Cov.:

AF XY:

0.00398

AC XY:

296

AN XY:

74400

show subpopulations

Gnomad4 AFR

AF:

0.0137

Gnomad4 AMR

AF:

0.00124

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00425

Alfa

AF:

0.00144

Hom.:

Bravo

AF:

0.00434

ESP6500AA

AF:

0.0152

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00114

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

May 01, 2023

PGAP2: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.26

CADD

Benign

DANN

Uncertain

0.99

Eigen

Uncertain

0.20

Eigen_PC

Benign

0.19

FATHMM_MKL

Benign

0.72

LIST_S2

Benign

0.15

T;T

MetaRNN

Benign

0.0045

T;T

MetaSVM

Benign

-0.94

MutationTaster

Benign

0.54

D;D;D;D;D;D

PrimateAI

Uncertain

0.63

PROVEAN

Benign

0.24

N;N

REVEL

Benign

0.15

Sift

Uncertain

0.0010

D;D

Polyphen

0.99

D;.

Vest4

0.46

MutPred

0.38

Gain of disorder (P = 0.0036);Gain of disorder (P = 0.0036);

MVP

0.49

ClinPred

0.095

GERP RS

3.1

Splicing

Name

Calibrated prediction

Score

Prediction

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