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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021259.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PGAP6	NM_021259.3	MANE Select	c.1577-21G>C		intron	N/A	NP_067082.2	Q9HCN3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PGAP6	ENST00000431232.7	TSL:1 MANE Select	c.1577-21G>C	intron	N/A	ENSP00000401338.2	Q9HCN3
PGAP6	ENST00000946607.1		c.1766-21G>C	intron	N/A	ENSP00000616666.1
PGAP6	ENST00000930879.1		c.1577-21G>C	intron	N/A	ENSP00000600938.1

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 v4.9

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

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over