17-39970658-AACAC-A

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_178171.5(GSDMA):​c.558+34_558+37delACAC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0155 in 1,347,884 control chromosomes in the GnomAD database, including 1,510 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.071 (1179 hom., cov: 0)
  • Exomes 𝑓: 0.0085 (331 hom.)
• Consequence: GSDMA NM_178171.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.334

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 -10 ACMG points.

• BP6: Variant 17-39970658-AACAC-A is Benign according to our data. Variant chr17-39970658-AACAC-A is described in ClinVar as [Benign]. Clinvar id is 402913.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.228 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GSDMA	NM_178171.5	c.558+34_558+37delACAC		intron_variant	Intron 4 of 11	ENST00000301659.9	NP_835465.2
GSDMA	XM_006721832.4	c.558+34_558+37delACAC		intron_variant	Intron 4 of 11		XP_006721895.1
GSDMA	XM_017024502.3	c.558+34_558+37delACAC		intron_variant	Intron 4 of 10		XP_016879991.1
GSDMA	XM_011524651.4	c.132+34_132+37delACAC		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+15delACAC		intron_variant	Intron 4 of 11	1	NM_178171.5	ENSP00000301659.4
GSDMA	ENST00000635792.1	c.558+12_558+15delACAC		intron_variant	Intron 4 of 11	5		ENSP00000490739.1
GSDMA	ENST00000577447.1	c.*94_*97delACAC		downstream_gene_variant		4		ENSP00000461985.1

Frequencies

GnomAD3 genomes AF: 0.0704 AC: 10605 AN: 150558 Hom.: 1173 Cov.: 0

Gnomad AFR AF: 0.232

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0435

Gnomad ASJ AF: 0.00493

Gnomad EAS AF: 0.000394

Gnomad SAS AF: 0.00527

Gnomad FIN AF: 0.000288

Gnomad MID AF: 0.0710

Gnomad NFE AF: 0.00339

Gnomad OTH AF: 0.0692

GnomAD2 exomes AF: 0.0212 AC: 1097 AN: 51756 AF XY: 0.0165

Gnomad AFR exome AF: 0.205

Gnomad AMR exome AF: 0.0255

Gnomad ASJ exome AF: 0.00675

Gnomad EAS exome AF: 0.000957

Gnomad FIN exome AF: 0.000635

Gnomad NFE exome AF: 0.00395

Gnomad OTH exome AF: 0.0159

GnomAD4 exome AF: 0.00852 AC: 10205 AN: 1197208 Hom.: 331 AF XY: 0.00791 AC XY: 4614 AN XY: 583130

African (AFR) AF: 0.221 AC: 5646 AN: 25566

American (AMR) AF: 0.0265 AC: 462 AN: 17430

Ashkenazi Jewish (ASJ) AF: 0.00652 AC: 115 AN: 17630

East Asian (EAS) AF: 0.000731 AC: 21 AN: 28720

South Asian (SAS) AF: 0.00349 AC: 196 AN: 56238

European-Finnish (FIN) AF: 0.000659 AC: 28 AN: 42520

Middle Eastern (MID) AF: 0.0308 AC: 111 AN: 3606

European-Non Finnish (NFE) AF: 0.00272 AC: 2604 AN: 956610

Other (OTH) AF: 0.0209 AC: 1022 AN: 48888

GnomAD4 genome AF: 0.0706 AC: 10634 AN: 150676 Hom.: 1179 Cov.: 0 AF XY: 0.0699 AC XY: 5138 AN XY: 73544

African (AFR) AF: 0.232 AC: 9538 AN: 41042

American (AMR) AF: 0.0434 AC: 659 AN: 15178

Ashkenazi Jewish (ASJ) AF: 0.00493 AC: 17 AN: 3448

East Asian (EAS) AF: 0.000394 AC: 2 AN: 5070

South Asian (SAS) AF: 0.00464 AC: 22 AN: 4744

European-Finnish (FIN) AF: 0.000288 AC: 3 AN: 10404

Middle Eastern (MID) AF: 0.0759 AC: 22 AN: 290

European-Non Finnish (NFE) AF: 0.00339 AC: 229 AN: 67518

Other (OTH) AF: 0.0680 AC: 142 AN: 2088

Alfa AF: 0.00836 Hom.: 981

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Computational scores

Source: dbNSFP v4.3

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

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs58338887; hg19: chr17-38126911;