Genetic Variant GSDMA:c.558+26_558+37delACACACACACAC (chr17-39970658-AACACACACACAC-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+26_558+37delACACACACACAC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000362 in 1,353,086 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000027 ( 0 hom., cov: 0)

Exomes 𝑓: 0.000037 ( 0 hom. )

Consequence

GSDMA
NM_178171.5 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.334

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
GSDMA	NM_178171.5 link	c.558+26_558+37delACACACACACAC	intron_variant	Intron 4 of 11	ENST00000301659.9	NP_835465.2	Q96QA5
GSDMA	XM_006721832.4 link	c.558+26_558+37delACACACACACAC	intron_variant	Intron 4 of 11		XP_006721895.1	Q96QA5
GSDMA	XM_017024502.3 link	c.558+26_558+37delACACACACACAC	intron_variant	Intron 4 of 10		XP_016879991.1
GSDMA	XM_011524651.4 link	c.132+26_132+37delACACACACACAC	intron_variant	Intron 2 of 9		XP_011522953.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
GSDMA	ENST00000301659.9 link	c.558+12_558+23delACACACACACAC	intron_variant	Intron 4 of 11	1	NM_178171.5	ENSP00000301659.4	Q96QA5
GSDMA	ENST00000635792.1 link	c.558+12_558+23delACACACACACAC	intron_variant	Intron 4 of 11	5		ENSP00000490739.1	Q96QA5
GSDMA	ENST00000577447.1 link	c.94_105delACACACACACAC	downstream_gene_variant		4		ENSP00000461985.1	J3KRG2

Frequencies

GnomAD3 genomes

AF:

0.0000266

AC:

AN:

150620

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000976

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000374

AC:

AN:

1202344

Hom.:

AF XY:

0.0000427

AC XY:

AN XY:

585612

show subpopulations

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

African (AFR)

AF:

0.000156

AC:

AN:

25666

American (AMR)

AF:

0.000114

AC:

AN:

17496

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

17702

East Asian (EAS)

AF:

0.0000696

AC:

AN:

28750

South Asian (SAS)

AF:

0.0000530

AC:

AN:

56604

European-Finnish (FIN)

AF:

0.0000469

AC:

AN:

42646

Middle Eastern (MID)

AF:

0.000275

AC:

AN:

3630

European-Non Finnish (NFE)

AF:

0.0000281

AC:

AN:

960748

Other (OTH)

AF:

0.0000815

AC:

AN:

49102

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.291

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000265

AC:

AN:

150742

Hom.:

Cov.:

AF XY:

0.0000272

AC XY:

AN XY:

73572

show subpopulations

African (AFR)

AF:

0.0000973

AC:

AN:

41106

American (AMR)

AF:

0.00

AC:

AN:

15178

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3448

East Asian (EAS)

AF:

0.00

AC:

AN:

5070

South Asian (SAS)

AF:

0.00

AC:

AN:

4744

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10402

Middle Eastern (MID)

AF:

0.00

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67522

Other (OTH)

AF:

0.00

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

981

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.33

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

17-39970658-AACACACACACACACAC-AACAC

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over