Genetic Variant PGAP6:p.Ile310Val (chr16-376432-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_021259.3(PGAP6):c.928A>G(p.Ile310Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.57 in 1,581,270 control chromosomes in the GnomAD database, including 260,426 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.57 ( 25112 hom., cov: 34)

Exomes 𝑓: 0.57 ( 235314 hom. )

Consequence

PGAP6
NM_021259.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.26

Publications

50 publications found

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 was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.7885794E-6).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.678 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PGAP6	NM_021259.3 link	c.928A>G	p.Ile310Val	missense_variant	Exon 6 of 13	ENST00000431232.7	NP_067082.2
PGAP6	XM_047434413.1 link	c.349A>G	p.Ile117Val	missense_variant	Exon 7 of 14		XP_047290369.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
PGAP6	ENST00000431232.7 link	c.928A>G	p.Ile310Val	missense_variant	Exon 6 of 13	1	NM_021259.3	ENSP00000401338.2
PGAP6	ENST00000250930.7 link	c.349A>G	p.Ile117Val	missense_variant	Exon 6 of 13	2		ENSP00000250930.3
PGAP6	ENST00000475348.1 link	n.44A>G		non_coding_transcript_exon_variant	Exon 1 of 4	2

Frequencies

GnomAD3 genomes

AF:

0.569

AC:

86541

AN:

152056

Hom.:

25083

Cov.:

show subpopulations

Gnomad AFR

AF:

0.636

Gnomad AMI

AF:

0.575

Gnomad AMR

AF:

0.487

Gnomad ASJ

AF:

0.438

Gnomad EAS

AF:

0.314

Gnomad SAS

AF:

0.695

Gnomad FIN

AF:

0.565

Gnomad MID

AF:

0.462

Gnomad NFE

AF:

0.567

Gnomad OTH

AF:

0.520

GnomAD2 exomes

AF:

0.535

AC:

119652

AN:

223568

AF XY:

0.548

show subpopulations

Gnomad AFR exome

AF:

0.628

Gnomad AMR exome

AF:

0.415

Gnomad ASJ exome

AF:

0.441

Gnomad EAS exome

AF:

0.315

Gnomad FIN exome

AF:

0.558

Gnomad NFE exome

AF:

0.561

Gnomad OTH exome

AF:

0.538

GnomAD4 exome

AF:

0.570

AC:

814393

AN:

1429094

Hom.:

235314

Cov.:

AF XY:

0.573

AC XY:

405210

AN XY:

706706

show subpopulations

African (AFR)

AF:

0.641

AC:

21182

AN:

33022

American (AMR)

AF:

0.424

AC:

18136

AN:

42738

Ashkenazi Jewish (ASJ)

AF:

0.440

AC:

10491

AN:

23860

East Asian (EAS)

AF:

0.308

AC:

12137

AN:

39354

South Asian (SAS)

AF:

0.696

AC:

56551

AN:

81202

European-Finnish (FIN)

AF:

0.558

AC:

27984

AN:

50134

Middle Eastern (MID)

AF:

0.491

AC:

2742

AN:

5588

European-Non Finnish (NFE)

AF:

0.578

AC:

632276

AN:

1094138

Other (OTH)

AF:

0.557

AC:

32894

AN:

59058

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

21134

42269

63403

84538

105672

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17776

35552

53328

71104

88880

<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:

0.569

AC:

86633

AN:

152176

Hom.:

25112

Cov.:

AF XY:

0.569

AC XY:

42312

AN XY:

74392

show subpopulations

African (AFR)

AF:

0.636

AC:

26411

AN:

41536

American (AMR)

AF:

0.487

AC:

7439

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.438

AC:

1517

AN:

3466

East Asian (EAS)

AF:

0.314

AC:

1622

AN:

5164

South Asian (SAS)

AF:

0.698

AC:

3371

AN:

4830

European-Finnish (FIN)

AF:

0.565

AC:

5983

AN:

10596

Middle Eastern (MID)

AF:

0.463

AC:

136

AN:

294

European-Non Finnish (NFE)

AF:

0.567

AC:

38530

AN:

67988

Other (OTH)

AF:

0.522

AC:

1100

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1954

3909

5863

7818

9772

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

744

1488

2232

2976

3720

<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:

0.552

Hom.:

53074

Bravo

AF:

0.557

TwinsUK

AF:

0.591

AC:

2190

ALSPAC

AF:

0.580

AC:

2234

ESP6500AA

AF:

0.624

AC:

2746

ESP6500EA

AF:

0.567

AC:

4870

ExAC

AF:

0.539

AC:

65058

Asia WGS

AF:

0.541

AC:

1881

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.84

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.0050

(source)

DANN

Benign

0.073

DEOGEN2

Benign

0.0037

T;.

Eigen

Benign

-2.8

Eigen_PC

Benign

-2.9

FATHMM_MKL

Benign

0.036

LIST_S2

Benign

0.19

T;T

MetaRNN

Benign

0.0000018

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.1

N;.

PhyloP100

-2.3

PrimateAI

Benign

0.24

PROVEAN

Benign

-0.10

N;N

REVEL

Benign

0.0040

Sift

Benign

0.31

T;T

Sift4G

Benign

0.64

T;T

Polyphen

0.0

B;.

Vest4

0.029

MPC

0.037

ClinPred

0.032

GERP RS

-9.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.014

gMVP

0.32

Mutation Taster

=96/4

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Computational scores

Splicing

Publications

Other links and lift over