chr17-39970658-AACACACACACAC-A

Position:

• chr17-39970658-AACACACACACAC-A

Variant summary

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

The NM_178171.5(GSDMA):​c.558+26_558+37delACACACACACAC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000362 in 1,353,086 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000027 (0 hom., cov: 0)
  • Exomes 𝑓: 0.000037 (0 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	Protein	UniProt
GSDMA	NM_178171.5	c.558+26_558+37delACACACACACAC		intron_variant		ENST00000301659.9	NP_835465.2
GSDMA	XM_006721832.4	c.558+26_558+37delACACACACACAC		intron_variant			XP_006721895.1
GSDMA	XM_017024502.3	c.558+26_558+37delACACACACACAC		intron_variant			XP_016879991.1
GSDMA	XM_011524651.4	c.132+26_132+37delACACACACACAC		intron_variant			XP_011522953.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GSDMA	ENST00000301659.9	c.558+26_558+37delACACACACACAC		intron_variant		1	NM_178171.5	ENSP00000301659.4
GSDMA	ENST00000635792.1	c.558+26_558+37delACACACACACAC		intron_variant		5		ENSP00000490739.1

Frequencies

GnomAD3 genomes AF: 0.0000266 AC: 4 AN: 150620 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000976

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000374 AC: 45 AN: 1202344 Hom.: 0 AF XY: 0.0000427 AC XY: 25 AN XY: 585612

Gnomad4 AFR exome AF: 0.000156

Gnomad4 AMR exome AF: 0.000114

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000696

Gnomad4 SAS exome AF: 0.0000530

Gnomad4 FIN exome AF: 0.0000469

Gnomad4 NFE exome AF: 0.0000281

Gnomad4 OTH exome AF: 0.0000815

GnomAD4 genome AF: 0.0000265 AC: 4 AN: 150742 Hom.: 0 Cov.: 0 AF XY: 0.0000272 AC XY: 2 AN XY: 73572

Gnomad4 AFR AF: 0.0000973

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

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;