chr17-39970658-A-AAC

Variant names:

• chr17-39970658-A-AAC
• rs58338887
• NM_178171.5:c.558+36_558+37dupAC

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_178171.5(GSDMA):​c.558+36_558+37dupAC 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 0.0040 (2 hom., cov: 0)
  • Exomes 𝑓: 0.0060 (2 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: Likely_benign. The variant received -4 ACMG points.

• BS2: High Homozygotes in GnomAd4 at 2 AR gene

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+36_558+37dupAC		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+11_558+12insAC		intron	N/A	ENSP00000301659.4
	GSDMA	ENST00000635792.1	TSL:5	c.558+11_558+12insAC		intron	N/A	ENSP00000490739.1
	GSDMA	ENST00000577447.1	TSL:4	c.*93_*94insAC		downstream_gene	N/A	ENSP00000461985.1

Frequencies

GnomAD3 genomes AF: 0.00396 AC: 596 AN: 150608 Hom.: 2 Cov.: 0

Gnomad AFR AF: 0.00478

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00165

Gnomad ASJ AF: 0.00174

Gnomad EAS AF: 0.000787

Gnomad SAS AF: 0.00190

Gnomad FIN AF: 0.000385

Gnomad MID AF: 0.00323

Gnomad NFE AF: 0.00514

Gnomad OTH AF: 0.00194

GnomAD2 exomes AF: 0.00305 AC: 158 AN: 51756 AF XY: 0.00284

Gnomad AFR exome AF: 0.00437

Gnomad AMR exome AF: 0.00241

Gnomad ASJ exome AF: 0.00281

Gnomad EAS exome AF: 0.000638

Gnomad FIN exome AF: 0.000953

Gnomad NFE exome AF: 0.00466

Gnomad OTH exome AF: 0.00303

GnomAD4 exome AF: 0.00596 AC: 7159 AN: 1201914 Hom.: 2 Cov.: 0 AF XY: 0.00578 AC XY: 3383 AN XY: 585382

African (AFR) AF: 0.00440 AC: 113 AN: 25672

American (AMR) AF: 0.00200 AC: 35 AN: 17506

Ashkenazi Jewish (ASJ) AF: 0.00209 AC: 37 AN: 17704

East Asian (EAS) AF: 0.000451 AC: 13 AN: 28798

South Asian (SAS) AF: 0.00141 AC: 80 AN: 56546

European-Finnish (FIN) AF: 0.000961 AC: 41 AN: 42648

Middle Eastern (MID) AF: 0.00193 AC: 7 AN: 3630

European-Non Finnish (NFE) AF: 0.00694 AC: 6662 AN: 960314

Other (OTH) AF: 0.00348 AC: 171 AN: 49096

GnomAD4 genome AF: 0.00395 AC: 596 AN: 150730 Hom.: 2 Cov.: 0 AF XY: 0.00352 AC XY: 259 AN XY: 73562

African (AFR) AF: 0.00477 AC: 196 AN: 41100

American (AMR) AF: 0.00165 AC: 25 AN: 15178

Ashkenazi Jewish (ASJ) AF: 0.00174 AC: 6 AN: 3448

East Asian (EAS) AF: 0.000789 AC: 4 AN: 5070

South Asian (SAS) AF: 0.00190 AC: 9 AN: 4742

European-Finnish (FIN) AF: 0.000385 AC: 4 AN: 10402

Middle Eastern (MID) AF: 0.00345 AC: 1 AN: 290

European-Non Finnish (NFE) AF: 0.00514 AC: 347 AN: 67518

Other (OTH) AF: 0.00192 AC: 4 AN: 2088

Alfa AF: 0.00211 Hom.: 981

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.83
Mutation Taster		=100/0	polymorphism

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;