Genetic Variant PGAP6:c.1577-21G>C (chr16-374420-C-G) – 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.1577-21G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.577 in 1,543,268 control chromosomes in the GnomAD database, including 260,227 homozygotes. In-silico tool predicts 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 ( 25301 hom., cov: 33)

Exomes 𝑓: 0.58 ( 234926 hom. )

Consequence

PGAP6
NM_021259.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.536

Publications

17 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 (BayesDel_noAF=-0.96).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.688 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PGAP6	NM_021259.3 link	c.1577-21G>C		intron_variant	Intron 9 of 12	ENST00000431232.7	NP_067082.2	Q9HCN3
PGAP6	XM_047434413.1 link	c.998-21G>C		intron_variant	Intron 10 of 13		XP_047290369.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PGAP6	ENST00000431232.7 link	c.1577-21G>C		intron_variant	Intron 9 of 12	1	NM_021259.3	ENSP00000401338.2		Q9HCN3

Frequencies

GnomAD3 genomes

AF:

0.572

AC:

86789

AN:

151808

Hom.:

25269

Cov.:

show subpopulations

Gnomad AFR

AF:

0.629

Gnomad AMI

AF:

0.576

Gnomad AMR

AF:

0.496

Gnomad ASJ

AF:

0.440

Gnomad EAS

AF:

0.314

Gnomad SAS

AF:

0.706

Gnomad FIN

AF:

0.568

Gnomad MID

AF:

0.459

Gnomad NFE

AF:

0.573

Gnomad OTH

AF:

0.522

GnomAD2 exomes

AF:

0.542

AC:

106738

AN:

196782

AF XY:

0.555

show subpopulations

Gnomad AFR exome

AF:

0.622

Gnomad AMR exome

AF:

0.435

Gnomad ASJ exome

AF:

0.448

Gnomad EAS exome

AF:

0.316

Gnomad FIN exome

AF:

0.559

Gnomad NFE exome

AF:

0.566

Gnomad OTH exome

AF:

0.545

GnomAD4 exome

AF:

0.577

AC:

803286

AN:

1391342

Hom.:

234926

Cov.:

AF XY:

0.581

AC XY:

398633

AN XY:

686146

show subpopulations

African (AFR)

AF:

0.634

AC:

20308

AN:

32038

American (AMR)

AF:

0.444

AC:

17161

AN:

38676

Ashkenazi Jewish (ASJ)

AF:

0.444

AC:

10157

AN:

22900

East Asian (EAS)

AF:

0.320

AC:

12479

AN:

38962

South Asian (SAS)

AF:

0.708

AC:

55898

AN:

78930

European-Finnish (FIN)

AF:

0.560

AC:

20858

AN:

37214

Middle Eastern (MID)

AF:

0.500

AC:

1982

AN:

3962

European-Non Finnish (NFE)

AF:

0.585

AC:

632121

AN:

1081032

Other (OTH)

AF:

0.561

AC:

32322

AN:

57628

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

15430

30861

46291

61722

77152

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17844

35688

53532

71376

89220

<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:

0.572

AC:

86882

AN:

151926

Hom.:

25301

Cov.:

AF XY:

0.571

AC XY:

42376

AN XY:

74228

show subpopulations

African (AFR)

AF:

0.629

AC:

26078

AN:

41442

American (AMR)

AF:

0.495

AC:

7568

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.440

AC:

1526

AN:

3468

East Asian (EAS)

AF:

0.314

AC:

1619

AN:

5148

South Asian (SAS)

AF:

0.708

AC:

3410

AN:

4818

European-Finnish (FIN)

AF:

0.568

AC:

5988

AN:

10544

Middle Eastern (MID)

AF:

0.466

AC:

137

AN:

294

European-Non Finnish (NFE)

AF:

0.573

AC:

38931

AN:

67918

Other (OTH)

AF:

0.523

AC:

1102

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

1884

3768

5651

7535

9419

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

742

1484

2226

2968

3710

<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:

0.472

Hom.:

2331

Bravo

AF:

0.559

Asia WGS

AF:

0.544

AC:

1890

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

0.44

(source)

DANN

Benign

0.50

PhyloP100

-0.54

PromoterAI

0.0053

Neutral

(source)

Mutation Taster

=100/0

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