chr17-39970658-AACACACAC-A

Variant names:

• chr17-39970658-AACACACAC-A
• rs58338887
• NM_178171.5:c.558+30_558+37delACACACAC

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_178171.5(GSDMA):​c.558+30_558+37delACACACAC 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
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.47 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178171.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSDMA	NM_178171.5	MANE Select	c.558+30_558+37delACACACAC		intron	N/A	NP_835465.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSDMA	ENST00000301659.9	TSL:1 MANE Select	c.558+12_558+19delACACACAC		intron	N/A	ENSP00000301659.4
	GSDMA	ENST00000635792.1	TSL:5	c.558+12_558+19delACACACAC		intron	N/A	ENSP00000490739.1
	GSDMA	ENST00000577447.1	TSL:4	c.*94_*101delACACACAC		downstream_gene	N/A	ENSP00000461985.1

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

GnomAD2 exomes AF: 0.391 AC: 20225 AN: 51756 AF XY: 0.386

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 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

African (AFR) AF: 0.306 AC: 7779 AN: 25388

American (AMR) AF: 0.378 AC: 6305 AN: 16680

Ashkenazi Jewish (ASJ) AF: 0.379 AC: 6378 AN: 16840

East Asian (EAS) AF: 0.488 AC: 13541 AN: 27766

South Asian (SAS) AF: 0.285 AC: 15422 AN: 54134

European-Finnish (FIN) AF: 0.378 AC: 15661 AN: 41478

Middle Eastern (MID) AF: 0.331 AC: 1104 AN: 3336

European-Non Finnish (NFE) AF: 0.409 AC: 380337 AN: 930458

Other (OTH) AF: 0.400 AC: 18919 AN: 47310

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

African (AFR) AF: 0.326 AC: 13380 AN: 41068

American (AMR) AF: 0.380 AC: 5765 AN: 15158

Ashkenazi Jewish (ASJ) AF: 0.386 AC: 1331 AN: 3448

East Asian (EAS) AF: 0.486 AC: 2462 AN: 5064

South Asian (SAS) AF: 0.270 AC: 1279 AN: 4736

European-Finnish (FIN) AF: 0.390 AC: 4055 AN: 10394

Middle Eastern (MID) AF: 0.300 AC: 87 AN: 290

European-Non Finnish (NFE) AF: 0.424 AC: 28610 AN: 67442

Other (OTH) AF: 0.371 AC: 774 AN: 2084

Alfa AF: 0.361 Hom.: 981

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.33
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs58338887; hg19: chr17-38126911;