17-39970658-A-AAC

Position:

• chr17-39970658-A-AAC

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_178171.5(GSDMA):​c.558+36_558+37dup variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0040 (2 hom., cov: 0)
  • Exomes 𝑓: 0.0060 (2 hom.)
• Consequence: GSDMA NM_178171.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.827

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 Likely_benign. Variant got -4 ACMG points.

• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GSDMA	NM_178171.5	c.558+36_558+37dup		intron_variant		ENST00000301659.9
GSDMA	XM_006721832.4	c.558+36_558+37dup		intron_variant
GSDMA	XM_011524651.4	c.132+36_132+37dup		intron_variant
GSDMA	XM_017024502.3	c.558+36_558+37dup		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GSDMA	ENST00000301659.9	c.558+36_558+37dup		intron_variant		1	NM_178171.5	P1
GSDMA	ENST00000635792.1	c.558+36_558+37dup		intron_variant		5		P1

Frequencies

GnomAD3 genomes AF: 0.00396 AC: 596 AN: 150608 Hom.: 2 Cov.: 0

Gnomad AFR AF: 0.00478

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00165

Gnomad ASJ AF: 0.00174

Gnomad EAS AF: 0.000787

Gnomad SAS AF: 0.00190

Gnomad FIN AF: 0.000385

Gnomad MID AF: 0.00323

Gnomad NFE AF: 0.00514

Gnomad OTH AF: 0.00194

GnomAD3 exomes AF: 0.00305 AC: 158 AN: 51756 Hom.: 0 AF XY: 0.00284 AC XY: 72 AN XY: 25320

Gnomad AFR exome AF: 0.00437

Gnomad AMR exome AF: 0.00241

Gnomad ASJ exome AF: 0.00281

Gnomad EAS exome AF: 0.000638

Gnomad SAS exome AF: 0.00149

Gnomad FIN exome AF: 0.000953

Gnomad NFE exome AF: 0.00466

Gnomad OTH exome AF: 0.00303

GnomAD4 exome AF: 0.00596 AC: 7159 AN: 1201914 Hom.: 2 Cov.: 0 AF XY: 0.00578 AC XY: 3383 AN XY: 585382

Gnomad4 AFR exome AF: 0.00440

Gnomad4 AMR exome AF: 0.00200

Gnomad4 ASJ exome AF: 0.00209

Gnomad4 EAS exome AF: 0.000451

Gnomad4 SAS exome AF: 0.00141

Gnomad4 FIN exome AF: 0.000961

Gnomad4 NFE exome AF: 0.00694

Gnomad4 OTH exome AF: 0.00348

GnomAD4 genome AF: 0.00395 AC: 596 AN: 150730 Hom.: 2 Cov.: 0 AF XY: 0.00352 AC XY: 259 AN XY: 73562

Gnomad4 AFR AF: 0.00477

Gnomad4 AMR AF: 0.00165

Gnomad4 ASJ AF: 0.00174

Gnomad4 EAS AF: 0.000789

Gnomad4 SAS AF: 0.00190

Gnomad4 FIN AF: 0.000385

Gnomad4 NFE AF: 0.00514

Gnomad4 OTH AF: 0.00192

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;