17-39970658-AACACACACACACACAC-AACACACACAC

Variant names:

• chr17-39970658-AACACAC-A
• rs58338887
• NM_178171.5:c.558+32_558+37delACACAC

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_178171.5(GSDMA):​c.558+32_558+37delACACAC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.322 in 1,346,552 control chromosomes in the GnomAD database, including 46,053 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.32 (7915 hom., cov: 0)
  • Exomes 𝑓: 0.32 (38138 hom.)
• Consequence: GSDMA NM_178171.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.334
• Publications: 2 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.432 is higher than 0.05.

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+32_558+37delACACAC		intron	N/A	NP_835465.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSDMA	ENST00000301659.9	TSL:1 MANE Select	c.558+12_558+17delACACAC		intron	N/A	ENSP00000301659.4
	GSDMA	ENST00000635792.1	TSL:5	c.558+12_558+17delACACAC		intron	N/A	ENSP00000490739.1
	GSDMA	ENST00000577447.1	TSL:4	c.*94_*99delACACAC		downstream_gene	N/A	ENSP00000461985.1

Frequencies

GnomAD3 genomes AF: 0.316 AC: 47610 AN: 150490 Hom.: 7917 Cov.: 0

Gnomad AFR AF: 0.199

Gnomad AMI AF: 0.328

Gnomad AMR AF: 0.391

Gnomad ASJ AF: 0.414

Gnomad EAS AF: 0.397

Gnomad SAS AF: 0.448

Gnomad FIN AF: 0.306

Gnomad MID AF: 0.477

Gnomad NFE AF: 0.350

Gnomad OTH AF: 0.352

GnomAD2 exomes AF: 0.334 AC: 17272 AN: 51756 AF XY: 0.337

Gnomad AFR exome AF: 0.197

Gnomad AMR exome AF: 0.425

Gnomad ASJ exome AF: 0.378

Gnomad EAS exome AF: 0.363

Gnomad FIN exome AF: 0.301

Gnomad NFE exome AF: 0.328

Gnomad OTH exome AF: 0.343

GnomAD4 exome AF: 0.322 AC: 385423 AN: 1195940 Hom.: 38138 AF XY: 0.324 AC XY: 189015 AN XY: 582570

African (AFR) AF: 0.189 AC: 4747 AN: 25116

American (AMR) AF: 0.385 AC: 6708 AN: 17402

Ashkenazi Jewish (ASJ) AF: 0.366 AC: 6458 AN: 17630

East Asian (EAS) AF: 0.311 AC: 8923 AN: 28650

South Asian (SAS) AF: 0.391 AC: 21965 AN: 56246

European-Finnish (FIN) AF: 0.277 AC: 11787 AN: 42506

Middle Eastern (MID) AF: 0.461 AC: 1664 AN: 3606

European-Non Finnish (NFE) AF: 0.321 AC: 307209 AN: 955930

Other (OTH) AF: 0.327 AC: 15962 AN: 48854

GnomAD4 genome AF: 0.316 AC: 47634 AN: 150612 Hom.: 7915 Cov.: 0 AF XY: 0.317 AC XY: 23280 AN XY: 73500

African (AFR) AF: 0.200 AC: 8200 AN: 41060

American (AMR) AF: 0.390 AC: 5915 AN: 15162

Ashkenazi Jewish (ASJ) AF: 0.414 AC: 1425 AN: 3446

East Asian (EAS) AF: 0.397 AC: 2011 AN: 5066

South Asian (SAS) AF: 0.447 AC: 2120 AN: 4738

European-Finnish (FIN) AF: 0.306 AC: 3182 AN: 10394

Middle Eastern (MID) AF: 0.476 AC: 136 AN: 286

European-Non Finnish (NFE) AF: 0.350 AC: 23618 AN: 67478

Other (OTH) AF: 0.352 AC: 734 AN: 2088

Alfa AF: 0.320 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 (auto)

Splicing

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

Other links and lift over

dbSNP: rs58338887; hg19: chr17-38126911;