Genetic Variant GSDMA:c.558+36_558+37delAC (chr17-39970658-AAC-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+36_558+37delAC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00666 in 1,340,454 control chromosomes in the GnomAD database, including 2 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0017 ( 1 hom., cov: 0)

Exomes 𝑓: 0.0073 ( 1 hom. )

Consequence

GSDMA
NM_178171.5 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.00200

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+36_558+37delAC	intron_variant	Intron 4 of 11	ENST00000301659.9	NP_835465.2
GSDMA	XM_006721832.4 link	c.558+36_558+37delAC	intron_variant	Intron 4 of 11		XP_006721895.1
GSDMA	XM_017024502.3 link	c.558+36_558+37delAC	intron_variant	Intron 4 of 10		XP_016879991.1
GSDMA	XM_011524651.4 link	c.132+36_132+37delAC	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+13delAC	intron_variant	Intron 4 of 11	1	NM_178171.5	ENSP00000301659.4
GSDMA	ENST00000635792.1 link	c.558+12_558+13delAC	intron_variant	Intron 4 of 11	5		ENSP00000490739.1
GSDMA	ENST00000577447.1 link	c.94_95delAC	downstream_gene_variant		4		ENSP00000461985.1

Frequencies

GnomAD3 genomes

AF:

0.00171

AC:

257

AN:

150576

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00166

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000330

Gnomad ASJ

AF:

0.000870

Gnomad EAS

AF:

0.000197

Gnomad SAS

AF:

0.00126

Gnomad FIN

AF:

0.000385

Gnomad MID

AF:

0.00323

Gnomad NFE

AF:

0.00244

Gnomad OTH

AF:

0.00194

GnomAD2 exomes

AF:

0.0113

AC:

587

AN:

51756

AF XY:

0.0118

show subpopulations

Gnomad AFR exome

AF:

0.0128

Gnomad AMR exome

AF:

0.00385

Gnomad ASJ exome

AF:

0.00787

Gnomad EAS exome

AF:

0.00446

Gnomad FIN exome

AF:

0.0187

Gnomad NFE exome

AF:

0.0109

Gnomad OTH exome

AF:

0.0113

GnomAD4 exome

AF:

0.00729

AC:

8669

AN:

1189756

Hom.:

AF XY:

0.00741

AC XY:

4293

AN XY:

579402

show subpopulations

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

African (AFR)

AF:

0.00847

AC:

214

AN:

25274

American (AMR)

AF:

0.00436

AC:

AN:

17440

Ashkenazi Jewish (ASJ)

AF:

0.00685

AC:

120

AN:

17514

East Asian (EAS)

AF:

0.00298

AC:

AN:

28520

South Asian (SAS)

AF:

0.0103

AC:

577

AN:

55950

European-Finnish (FIN)

AF:

0.0133

AC:

551

AN:

41530

Middle Eastern (MID)

AF:

0.00361

AC:

AN:

3606

European-Non Finnish (NFE)

AF:

0.00707

AC:

6726

AN:

951330

Other (OTH)

AF:

0.00632

AC:

307

AN:

48592

⚠️ 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: 0.321

Heterozygous variant carriers

688

1377

2065

2754

3442

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

248

496

744

992

1240

<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:

0.00170

AC:

256

AN:

150698

Hom.:

Cov.:

AF XY:

0.00159

AC XY:

117

AN XY:

73554

show subpopulations

African (AFR)

AF:

0.00165

AC:

AN:

41102

American (AMR)

AF:

0.000329

AC:

AN:

15178

Ashkenazi Jewish (ASJ)

AF:

0.000870

AC:

AN:

3448

East Asian (EAS)

AF:

0.00

AC:

AN:

5070

South Asian (SAS)

AF:

0.00126

AC:

AN:

4744

European-Finnish (FIN)

AF:

0.000385

AC:

AN:

10380

Middle Eastern (MID)

AF:

0.00345

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.00244

AC:

165

AN:

67504

Other (OTH)

AF:

0.00192

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

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:

0.00865

Hom.:

981

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.0020

Mutation Taster

=100/0

polymorphism

(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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17-39970658-AACACACACACACACAC-AACACACACACACAC

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