Genetic Variant PGAP6:p.Thr136Ala (chr16-377479-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.406A>G(p.Thr136Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.571 in 1,607,742 control chromosomes in the GnomAD database, including 266,285 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 ( 25186 hom., cov: 33)

Exomes 𝑓: 0.57 ( 241099 hom. )

Consequence

PGAP6
NM_021259.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.23

Publications

46 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=1.234334E-5).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.685 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PGAP6	NM_021259.3 link	c.406A>G	p.Thr136Ala	missense_variant	Exon 3 of 13	ENST00000431232.7	NP_067082.2	Q9HCN3
PGAP6	XM_047434413.1 link	c.-174A>G		5_prime_UTR_variant	Exon 4 of 14		XP_047290369.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
PGAP6	ENST00000431232.7 link	c.406A>G	p.Thr136Ala	missense_variant	Exon 3 of 13	1	NM_021259.3	ENSP00000401338.2	Q9HCN3
PGAP6	ENST00000476735.1 link	n.643A>G		non_coding_transcript_exon_variant	Exon 4 of 5	5
PGAP6	ENST00000250930.7 link	c.-174A>G		5_prime_UTR_variant	Exon 3 of 13	2		ENSP00000250930.3	K4DI83
PGAP6	ENST00000427313.5 link	c.-174A>G		5_prime_UTR_variant	Exon 3 of 5	4		ENSP00000410987.1	C9J8D7

Frequencies

GnomAD3 genomes

AF:

0.571

AC:

86635

AN:

151786

Hom.:

25157

Cov.:

show subpopulations

Gnomad AFR

AF:

0.637

Gnomad AMI

AF:

0.578

Gnomad AMR

AF:

0.489

Gnomad ASJ

AF:

0.438

Gnomad EAS

AF:

0.311

Gnomad SAS

AF:

0.702

Gnomad FIN

AF:

0.567

Gnomad MID

AF:

0.459

Gnomad NFE

AF:

0.568

Gnomad OTH

AF:

0.521

GnomAD2 exomes

AF:

0.538

AC:

128380

AN:

238422

AF XY:

0.553

show subpopulations

Gnomad AFR exome

AF:

0.629

Gnomad AMR exome

AF:

0.415

Gnomad ASJ exome

AF:

0.438

Gnomad EAS exome

AF:

0.309

Gnomad FIN exome

AF:

0.555

Gnomad NFE exome

AF:

0.562

Gnomad OTH exome

AF:

0.536

GnomAD4 exome

AF:

0.571

AC:

831857

AN:

1455840

Hom.:

241099

Cov.:

AF XY:

0.575

AC XY:

416365

AN XY:

723736

show subpopulations

African (AFR)

AF:

0.642

AC:

21455

AN:

33434

American (AMR)

AF:

0.425

AC:

18736

AN:

44058

Ashkenazi Jewish (ASJ)

AF:

0.440

AC:

11434

AN:

26008

East Asian (EAS)

AF:

0.306

AC:

12109

AN:

39554

South Asian (SAS)

AF:

0.707

AC:

60473

AN:

85510

European-Finnish (FIN)

AF:

0.558

AC:

28800

AN:

51648

Middle Eastern (MID)

AF:

0.495

AC:

2848

AN:

5748

European-Non Finnish (NFE)

AF:

0.579

AC:

642551

AN:

1109782

Other (OTH)

AF:

0.557

AC:

33451

AN:

60098

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

21588

43176

64763

86351

107939

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17826

35652

53478

71304

89130

<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:

0.571

AC:

86727

AN:

151902

Hom.:

25186

Cov.:

AF XY:

0.571

AC XY:

42376

AN XY:

74254

show subpopulations

African (AFR)

AF:

0.637

AC:

26406

AN:

41452

American (AMR)

AF:

0.488

AC:

7465

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.438

AC:

1517

AN:

3464

East Asian (EAS)

AF:

0.312

AC:

1596

AN:

5120

South Asian (SAS)

AF:

0.704

AC:

3398

AN:

4824

European-Finnish (FIN)

AF:

0.567

AC:

5992

AN:

10574

Middle Eastern (MID)

AF:

0.463

AC:

136

AN:

294

European-Non Finnish (NFE)

AF:

0.569

AC:

38588

AN:

67870

Other (OTH)

AF:

0.522

AC:

1104

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.520

Heterozygous variant carriers

1951

3901

5852

7802

9753

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.:

41018

Bravo

AF:

0.557

TwinsUK

AF:

0.593

AC:

2199

ALSPAC

AF:

0.581

AC:

2240

ESP6500AA

AF:

0.623

AC:

2729

ESP6500EA

AF:

0.567

AC:

4876

ExAC

AF:

0.538

AC:

64606

Asia WGS

AF:

0.539

AC:

1873

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.057

BayesDel_addAF

Benign

-0.84

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.018

(source)

DANN

Benign

0.21

DEOGEN2

Benign

0.0033

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.050

LIST_S2

Benign

0.18

MetaRNN

Benign

0.000012

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.34

PhyloP100

-1.2

PrimateAI

Benign

0.33

PROVEAN

Benign

0.16

REVEL

Benign

0.019

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.0080

MPC

0.041

ClinPred

0.0017

GERP RS

0.98

Varity_R

0.013

gMVP

0.26

Mutation Taster

=298/2

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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