17-39970658-AACACACACACACAC-AACAC

Position:

• chr17-39970658-AACACACACACACAC-AACAC

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_178171.5(GSDMA):​c.558+28_558+37del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00245 in 1,315,166 control chromosomes in the GnomAD database, including 1 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00029 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0027 (1 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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GSDMA	NM_178171.5	c.558+28_558+37del		intron_variant		ENST00000301659.9
GSDMA	XM_006721832.4	c.558+28_558+37del		intron_variant
GSDMA	XM_011524651.4	c.132+28_132+37del		intron_variant
GSDMA	XM_017024502.3	c.558+28_558+37del		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GSDMA	ENST00000301659.9	c.558+28_558+37del		intron_variant		1	NM_178171.5	P1
GSDMA	ENST00000635792.1	c.558+28_558+37del		intron_variant		5		P1

Frequencies

GnomAD3 genomes AF: 0.000259 AC: 39 AN: 150600 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000439

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000726

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000590

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000104

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.00711 AC: 368 AN: 51756 Hom.: 0 AF XY: 0.00739 AC XY: 187 AN XY: 25320

Gnomad AFR exome AF: 0.00591

Gnomad AMR exome AF: 0.00642

Gnomad ASJ exome AF: 0.00675

Gnomad EAS exome AF: 0.0179

Gnomad SAS exome AF: 0.00595

Gnomad FIN exome AF: 0.00646

Gnomad NFE exome AF: 0.00650

Gnomad OTH exome AF: 0.00756

GnomAD4 exome AF: 0.00273 AC: 3182 AN: 1164444 Hom.: 1 AF XY: 0.00281 AC XY: 1594 AN XY: 567034

Gnomad4 AFR exome AF: 0.00250

Gnomad4 AMR exome AF: 0.00602

Gnomad4 ASJ exome AF: 0.00316

Gnomad4 EAS exome AF: 0.00593

Gnomad4 SAS exome AF: 0.00326

Gnomad4 FIN exome AF: 0.00401

Gnomad4 NFE exome AF: 0.00244

Gnomad4 OTH exome AF: 0.00377

GnomAD4 genome AF: 0.000292 AC: 44 AN: 150722 Hom.: 0 Cov.: 0 AF XY: 0.000231 AC XY: 17 AN XY: 73558

Gnomad4 AFR AF: 0.000438

Gnomad4 AMR AF: 0.000725

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000592

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000104

Gnomad4 OTH AF: 0.00239

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;