dbSNP rs11248931: 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

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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