Variant 16-372085-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_021259.3(PGAP6):c.2218C>A(p.Pro740Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00308 in 1,612,596 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0018 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0032 ( 15 hom. )

Consequence

PGAP6
NM_021259.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.409

Variant links:

Genes affected

PGAP6 (HGNC:17205): (post-GPI attachment to proteins 6) Predicted to enable phospholipase A2 activity. Located in extracellular exosome and lysosomal membrane. [provided by Alliance of Genome Resources, Apr 2022]

PGAP6 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.003340304).

BP6

Variant 16-372085-G-T is Benign according to our data. Variant chr16-372085-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 2645788.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 15 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PGAP6	NM_021259.3 linkuse as main transcript	c.2218C>A	p.Pro740Thr	missense_variant	13/13	ENST00000431232.7	NP_067082.2	Q9HCN3
PGAP6	XM_047434413.1 linkuse as main transcript	c.1639C>A	p.Pro547Thr	missense_variant	14/14		XP_047290369.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PGAP6	ENST00000431232.7 linkuse as main transcript	c.2218C>A	p.Pro740Thr	missense_variant	13/13	1	NM_021259.3	ENSP00000401338.2	Q9HCN3
PGAP6	ENST00000250930.7 linkuse as main transcript	c.1639C>A	p.Pro547Thr	missense_variant	13/13	2		ENSP00000250930.3	K4DI83
PGAP6	ENST00000424078.5 linkuse as main transcript	c.619C>A	p.Pro207Thr	missense_variant	4/4	3		ENSP00000397620.1	H0Y5B2

Frequencies

GnomAD3 genomes

AF:

0.00181

AC:

276

AN:

152152

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000628

Gnomad AMI

AF:

0.00877

Gnomad AMR

AF:

0.000785

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00186

Gnomad FIN

AF:

0.000376

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00307

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00201

AC:

503

AN:

249768

Hom.:

AF XY:

0.00229

AC XY:

311

AN XY:

135564

show subpopulations

Gnomad AFR exome

AF:

0.000559

Gnomad AMR exome

AF:

0.000463

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000218

Gnomad SAS exome

AF:

0.00235

Gnomad FIN exome

AF:

0.000140

Gnomad NFE exome

AF:

0.00344

Gnomad OTH exome

AF:

0.00180

GnomAD4 exome

AF:

0.00321

AC:

4694

AN:

1460326

Hom.:

Cov.:

AF XY:

0.00321

AC XY:

2331

AN XY:

726480

show subpopulations

Gnomad4 AFR exome

AF:

0.000627

Gnomad4 AMR exome

AF:

0.000649

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.00296

Gnomad4 FIN exome

AF:

0.000308

Gnomad4 NFE exome

AF:

0.00381

Gnomad4 OTH exome

AF:

0.00209

GnomAD4 genome

AF:

0.00181

AC:

275

AN:

152270

Hom.:

Cov.:

AF XY:

0.00158

AC XY:

118

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.000626

Gnomad4 AMR

AF:

0.000719

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00186

Gnomad4 FIN

AF:

0.000376

Gnomad4 NFE

AF:

0.00307

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00289

Hom.:

Bravo

AF:

0.00178

ESP6500AA

AF:

0.000909

AC:

ESP6500EA

AF:

0.00302

AC:

ExAC

AF:

0.00185

AC:

224

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.00278

EpiControl

AF:

0.00356

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

May 01, 2023

PGAP6: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.55

CADD

Benign

7.8

DANN

Benign

0.66

DEOGEN2

Benign

0.0097

T;.

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.17

LIST_S2

Benign

0.70

T;T

M_CAP

Benign

0.011

MetaRNN

Benign

0.0033

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

N;.

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.26

N;N

REVEL

Benign

0.028

Sift

Benign

0.24

T;T

Sift4G

Benign

0.20

T;T

Polyphen

0.10

B;.

Vest4

0.15

MVP

0.085

MPC

0.052

ClinPred

0.0032

GERP RS

1.0

Varity_R

0.023

gMVP

0.49

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