NM_178171.5:c.558+32_558+37dupACACAC

Variant names:

• chr17-39970658-A-AACACAC
• rs58338887
• NM_178171.5:c.558+32_558+37dupACACAC

Variant summary

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

The NM_178171.5(GSDMA):​c.558+32_558+37dupACACAC 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: not found (cov: 0)
  • Exomes 𝑓: 0.0000017 (0 hom.)
• Consequence: GSDMA NM_178171.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.827
• Publications: 0 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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSDMA	NM_178171.5	MANE Select	c.558+32_558+37dupACACAC		intron	N/A	NP_835465.2	Q96QA5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSDMA	ENST00000301659.9	TSL:1 MANE Select	c.558+11_558+12insACACAC		intron	N/A	ENSP00000301659.4	Q96QA5
	GSDMA	ENST00000635792.1	TSL:5	c.558+11_558+12insACACAC		intron	N/A	ENSP00000490739.1	Q96QA5
	GSDMA	ENST00000577447.1	TSL:4	c.*93_*94insACACAC		downstream_gene	N/A	ENSP00000461985.1	J3KRG2

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome AF: 0.00000166 AC: 2 AN: 1203374 Hom.: 0 Cov.: 0 AF XY: 0.00000171 AC XY: 1 AN XY: 586102

⚠️ 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: 17516

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 28804

South Asian (SAS) AF: 0.00 AC: 0 AN: 56648

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 42704

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

European-Non Finnish (NFE) AF: 0.00000208 AC: 2 AN: 961516

Other (OTH) AF: 0.00 AC: 0 AN: 49150

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000203476), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.83

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs58338887; hg19: chr17-38126911;