17-39970658-AACACACAC-A

Position:

• chr17-39970658-AACACACAC-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_178171.5(GSDMA):​c.558+30_558+37del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.398 in 1,313,966 control chromosomes in the GnomAD database, including 78,863 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.39 (11310 hom., cov: 0)
  • Exomes 𝑓: 0.40 (67553 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 (EAS) allele frequency at 95% confidence interval = 0.47 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GSDMA	NM_178171.5	c.558+30_558+37del		intron_variant		ENST00000301659.9
GSDMA	XM_006721832.4	c.558+30_558+37del		intron_variant
GSDMA	XM_011524651.4	c.132+30_132+37del		intron_variant
GSDMA	XM_017024502.3	c.558+30_558+37del		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GSDMA	ENST00000301659.9	c.558+30_558+37del		intron_variant		1	NM_178171.5	P1
GSDMA	ENST00000635792.1	c.558+30_558+37del		intron_variant		5		P1

Frequencies

GnomAD3 genomes AF: 0.386 AC: 58049 AN: 150454 Hom.: 11300 Cov.: 0

Gnomad AFR AF: 0.326

Gnomad AMI AF: 0.388

Gnomad AMR AF: 0.379

Gnomad ASJ AF: 0.386

Gnomad EAS AF: 0.486

Gnomad SAS AF: 0.269

Gnomad FIN AF: 0.390

Gnomad MID AF: 0.306

Gnomad NFE AF: 0.424

Gnomad OTH AF: 0.370

GnomAD3 exomes AF: 0.391 AC: 20225 AN: 51756 Hom.: 2972 AF XY: 0.386 AC XY: 9766 AN XY: 25320

Gnomad AFR exome AF: 0.321

Gnomad AMR exome AF: 0.377

Gnomad ASJ exome AF: 0.393

Gnomad EAS exome AF: 0.486

Gnomad SAS exome AF: 0.299

Gnomad FIN exome AF: 0.386

Gnomad NFE exome AF: 0.416

Gnomad OTH exome AF: 0.387

GnomAD4 exome AF: 0.400 AC: 465446 AN: 1163390 Hom.: 67553 AF XY: 0.397 AC XY: 224813 AN XY: 566052

Gnomad4 AFR exome AF: 0.306

Gnomad4 AMR exome AF: 0.378

Gnomad4 ASJ exome AF: 0.379

Gnomad4 EAS exome AF: 0.488

Gnomad4 SAS exome AF: 0.285

Gnomad4 FIN exome AF: 0.378

Gnomad4 NFE exome AF: 0.409

Gnomad4 OTH exome AF: 0.400

GnomAD4 genome AF: 0.386 AC: 58089 AN: 150576 Hom.: 11310 Cov.: 0 AF XY: 0.382 AC XY: 28033 AN XY: 73480

Gnomad4 AFR AF: 0.326

Gnomad4 AMR AF: 0.380

Gnomad4 ASJ AF: 0.386

Gnomad4 EAS AF: 0.486

Gnomad4 SAS AF: 0.270

Gnomad4 FIN AF: 0.390

Gnomad4 NFE AF: 0.424

Gnomad4 OTH AF: 0.371

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;