17-39970658-AACACACACACACAC-A

Variant names:

• chr17-39970658-AACACACACACACAC-A
• rs58338887
• NM_178171.5:c.558+24_558+37delACACACACACACAC

Variant summary

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

The NM_178171.5(GSDMA):​c.558+24_558+37delACACACACACACAC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000249 in 1,203,354 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 0)
  • Exomes 𝑓: 0.0000025 (0 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: 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+24_558+37delACACACACACACAC		intron_variant	Intron 4 of 11	ENST00000301659.9	NP_835465.2
GSDMA	XM_006721832.4	c.558+24_558+37delACACACACACACAC		intron_variant	Intron 4 of 11		XP_006721895.1
GSDMA	XM_017024502.3	c.558+24_558+37delACACACACACACAC		intron_variant	Intron 4 of 10		XP_016879991.1
GSDMA	XM_011524651.4	c.132+24_132+37delACACACACACACAC		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+12_558+25delACACACACACACAC		intron_variant	Intron 4 of 11	1	NM_178171.5	ENSP00000301659.4
GSDMA	ENST00000635792.1	c.558+12_558+25delACACACACACACAC		intron_variant	Intron 4 of 11	5		ENSP00000490739.1
GSDMA	ENST00000577447.1	c.*94_*107delACACACACACACAC		downstream_gene_variant		4		ENSP00000461985.1

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome AF: 0.00000249 AC: 3 AN: 1203354 Hom.: 0 AF XY: 0.00000171 AC XY: 1 AN XY: 586096

African (AFR) AF: 0.0000389 AC: 1 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: 961496

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

GnomAD4 genome Cov.: 0

Alfa AF: 0.00 Hom.: 981

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.33

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;