17-39970658-AACACACACACACACAC-AACACACACACACACACACAC

Variant names:

• chr17-39970658-A-AACAC
• rs58338887
• NM_178171.5:c.558+34_558+37dupACAC

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_178171.5(GSDMA):​c.558+34_558+37dupACAC 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 0.000086 (0 hom., cov: 0)
  • Exomes 𝑓: 0.000023 (0 hom.)
• Consequence: GSDMA NM_178171.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.827
• 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: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GSDMA	NM_178171.5	c.558+34_558+37dupACAC		intron_variant	Intron 4 of 11	ENST00000301659.9	NP_835465.2
GSDMA	XM_006721832.4	c.558+34_558+37dupACAC		intron_variant	Intron 4 of 11		XP_006721895.1
GSDMA	XM_017024502.3	c.558+34_558+37dupACAC		intron_variant	Intron 4 of 10		XP_016879991.1
GSDMA	XM_011524651.4	c.132+34_132+37dupACAC		intron_variant	Intron 2 of 9		XP_011522953.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GSDMA	ENST00000301659.9	c.558+11_558+12insACAC		intron_variant	Intron 4 of 11	1	NM_178171.5	ENSP00000301659.4
GSDMA	ENST00000635792.1	c.558+11_558+12insACAC		intron_variant	Intron 4 of 11	5		ENSP00000490739.1
GSDMA	ENST00000577447.1	c.*93_*94insACAC		downstream_gene_variant		4		ENSP00000461985.1

Frequencies

GnomAD3 genomes AF: 0.0000863 AC: 13 AN: 150622 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000732

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000528

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000197

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000148

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000233 AC: 28 AN: 1203340 Hom.: 0 Cov.: 0 AF XY: 0.0000205 AC XY: 12 AN XY: 586088

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 25690

American (AMR) AF: 0.00 AC: 0 AN: 17514

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17716

East Asian (EAS) AF: 0.0000347 AC: 1 AN: 28804

South Asian (SAS) AF: 0.00 AC: 0 AN: 56646

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 42702

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3630

European-Non Finnish (NFE) AF: 0.0000250 AC: 24 AN: 961490

Other (OTH) AF: 0.0000610 AC: 3 AN: 49148

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000106794), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0000863 AC: 13 AN: 150622 Hom.: 0 Cov.: 0 AF XY: 0.0000681 AC XY: 5 AN XY: 73442

African (AFR) AF: 0.0000732 AC: 3 AN: 40984

American (AMR) AF: 0.000528 AC: 8 AN: 15158

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3448

East Asian (EAS) AF: 0.000197 AC: 1 AN: 5082

South Asian (SAS) AF: 0.00 AC: 0 AN: 4746

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10404

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 310

European-Non Finnish (NFE) AF: 0.0000148 AC: 1 AN: 67530

Other (OTH) AF: 0.00 AC: 0 AN: 2066

Alfa AF: 0.00 Hom.: 981

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.83

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;