Genetic Variant NM_178171.5: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:

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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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSDMA	NM_178171.5	MANE Select	c.558+36_558+37delAC		intron	N/A	NP_835465.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
GSDMA	ENST00000301659.9	TSL:1 MANE Select	c.558+12_558+13delAC	intron	N/A	ENSP00000301659.4
GSDMA	ENST00000635792.1	TSL:5	c.558+12_558+13delAC	intron	N/A	ENSP00000490739.1
GSDMA	ENST00000577447.1	TSL:4	c.94_95delAC	downstream_gene	N/A	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 v4.9

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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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