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:

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ACMG classification

Classification was made for transcript

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178171.5. 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
	GSDMA	NM_178171.5	MANE Select	c.558+28_558+37delACACACACAC		intron	N/A	NP_835465.2	Q96QA5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
GSDMA	ENST00000301659.9	TSL:1 MANE Select	c.558+12_558+21delACACACACAC	intron	N/A	ENSP00000301659.4	Q96QA5
GSDMA	ENST00000635792.1	TSL:5	c.558+12_558+21delACACACACAC	intron	N/A	ENSP00000490739.1	Q96QA5
GSDMA	ENST00000577447.1	TSL:4	c.94_103delACACACACAC	downstream_gene	N/A	ENSP00000461985.1	J3KRG2

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 v4.9

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over