17-39970658-AACACACACACACAC-AACACACAC

Position:

• chr17-39970658-AACACACACACACAC-AACACACAC

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -8 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GSDMA	NM_178171.5	c.558+32_558+37delACACAC		intron_variant		ENST00000301659.9	NP_835465.2
GSDMA	XM_006721832.4	c.558+32_558+37delACACAC		intron_variant			XP_006721895.1
GSDMA	XM_017024502.3	c.558+32_558+37delACACAC		intron_variant			XP_016879991.1
GSDMA	XM_011524651.4	c.132+32_132+37delACACAC		intron_variant			XP_011522953.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GSDMA	ENST00000301659.9	c.558+32_558+37delACACAC		intron_variant		1	NM_178171.5	ENSP00000301659.4
GSDMA	ENST00000635792.1	c.558+32_558+37delACACAC		intron_variant		5		ENSP00000490739.1

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

GnomAD3 exomes AF: 0.334 AC: 17272 AN: 51756 Hom.: 2136 AF XY: 0.337 AC XY: 8542 AN XY: 25320

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 SAS exome AF: 0.380

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

Gnomad4 AFR exome AF: 0.189

Gnomad4 AMR exome AF: 0.385

Gnomad4 ASJ exome AF: 0.366

Gnomad4 EAS exome AF: 0.311

Gnomad4 SAS exome AF: 0.391

Gnomad4 FIN exome AF: 0.277

Gnomad4 NFE exome AF: 0.321

Gnomad4 OTH exome AF: 0.327

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

Gnomad4 AFR AF: 0.200

Gnomad4 AMR AF: 0.390

Gnomad4 ASJ AF: 0.414

Gnomad4 EAS AF: 0.397

Gnomad4 SAS AF: 0.447

Gnomad4 FIN AF: 0.306

Gnomad4 NFE AF: 0.350

Gnomad4 OTH AF: 0.352

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs58338887; hg19: chr17-38126911;