Genetic Variant GSDMA:c.558+28_558+37delACACACACAC (chr17-39970658-AACACACACAC-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_178171.5(GSDMA):c.558+28_558+37delACACACACAC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00245 in 1,315,166 control chromosomes in the GnomAD database, including 1 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00029 ( 0 hom., cov: 0)

Exomes 𝑓: 0.0027 ( 1 hom. )

Consequence

GSDMA
NM_178171.5 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.334

Publications

2 publications found

Variant links:

Genes affected

GSDMA (HGNC:13311): (gasdermin A) Predicted to enable phosphatidylinositol-4,5-bisphosphate binding activity; phosphatidylinositol-4-phosphate binding activity; and phosphatidylserine binding activity. Involved in apoptotic process. Located in perinuclear region of cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

GSDMA links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
GSDMA	NM_178171.5 link	c.558+28_558+37delACACACACAC	intron_variant	Intron 4 of 11	ENST00000301659.9	NP_835465.2
GSDMA	XM_006721832.4 link	c.558+28_558+37delACACACACAC	intron_variant	Intron 4 of 11		XP_006721895.1
GSDMA	XM_017024502.3 link	c.558+28_558+37delACACACACAC	intron_variant	Intron 4 of 10		XP_016879991.1
GSDMA	XM_011524651.4 link	c.132+28_132+37delACACACACAC	intron_variant	Intron 2 of 9		XP_011522953.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
GSDMA	ENST00000301659.9 link	c.558+12_558+21delACACACACAC	intron_variant	Intron 4 of 11	1	NM_178171.5	ENSP00000301659.4
GSDMA	ENST00000635792.1 link	c.558+12_558+21delACACACACAC	intron_variant	Intron 4 of 11	5		ENSP00000490739.1
GSDMA	ENST00000577447.1 link	c.94_103delACACACACAC	downstream_gene_variant		4		ENSP00000461985.1

Frequencies

GnomAD3 genomes

AF:

0.000259

AC:

AN:

150600

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000439

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000726

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000590

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000104

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00711

AC:

368

AN:

51756

AF XY:

0.00739

show subpopulations

Gnomad AFR exome

AF:

0.00591

Gnomad AMR exome

AF:

0.00642

Gnomad ASJ exome

AF:

0.00675

Gnomad EAS exome

AF:

0.0179

Gnomad FIN exome

AF:

0.00646

Gnomad NFE exome

AF:

0.00650

Gnomad OTH exome

AF:

0.00756

GnomAD4 exome

AF:

0.00273

AC:

3182

AN:

1164444

Hom.:

AF XY:

0.00281

AC XY:

1594

AN XY:

567034

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00250

AC:

AN:

25168

American (AMR)

AF:

0.00602

AC:

102

AN:

16954

Ashkenazi Jewish (ASJ)

AF:

0.00316

AC:

AN:

17110

East Asian (EAS)

AF:

0.00593

AC:

159

AN:

26792

South Asian (SAS)

AF:

0.00326

AC:

182

AN:

55772

European-Finnish (FIN)

AF:

0.00401

AC:

165

AN:

41096

Middle Eastern (MID)

AF:

0.00310

AC:

AN:

3546

European-Non Finnish (NFE)

AF:

0.00244

AC:

2267

AN:

930588

Other (OTH)

AF:

0.00377

AC:

179

AN:

47418

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.261

Heterozygous variant carriers

440

880

1319

1759

2199

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

128

192

256

320

<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:

0.000292

AC:

AN:

150722

Hom.:

Cov.:

AF XY:

0.000231

AC XY:

AN XY:

73558

show subpopulations

African (AFR)

AF:

0.000438

AC:

AN:

41102

American (AMR)

AF:

0.000725

AC:

AN:

15176

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3448

East Asian (EAS)

AF:

0.000592

AC:

AN:

5070

South Asian (SAS)

AF:

0.00

AC:

AN:

4744

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10394

Middle Eastern (MID)

AF:

0.00

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.000104

AC:

AN:

67516

Other (OTH)

AF:

0.00239

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00676

Hom.:

981

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.33

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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17-39970658-AACACACACACACACAC-AACACAC

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