rs56030650

Variant names:

• chr17-39974934-C-A
• rs56030650
• NM_178171.5:c.941C>A

Your query was ambiguous. Multiple possible variants found:

• chr17-39974934-C-A
• chr17-39974934-C-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_178171.5(GSDMA):​c.941C>A​(p.Thr314Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.446 in 1,606,720 control chromosomes in the GnomAD database, including 162,879 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.41 (13394 hom., cov: 31)
  • Exomes 𝑓: 0.45 (149485 hom.)
• Consequence: GSDMA NM_178171.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.48
• Publications: 44 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0031422079).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.468 is higher than 0.05.

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.941C>A	p.Thr314Asn	missense	Exon 10 of 12	NP_835465.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSDMA	ENST00000301659.9	TSL:1 MANE Select	c.941C>A	p.Thr314Asn	missense	Exon 10 of 12	ENSP00000301659.4
	GSDMA	ENST00000635792.1	TSL:5	c.941C>A	p.Thr314Asn	missense	Exon 10 of 12	ENSP00000490739.1

Frequencies

GnomAD3 genomes AF: 0.415 AC: 62978 AN: 151882 Hom.: 13385 Cov.: 31

Gnomad AFR AF: 0.333

Gnomad AMI AF: 0.463

Gnomad AMR AF: 0.395

Gnomad ASJ AF: 0.414

Gnomad EAS AF: 0.484

Gnomad SAS AF: 0.285

Gnomad FIN AF: 0.435

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.470

Gnomad OTH AF: 0.394

GnomAD2 exomes AF: 0.416 AC: 102249 AN: 246038 AF XY: 0.411

Gnomad AFR exome AF: 0.325

Gnomad AMR exome AF: 0.375

Gnomad ASJ exome AF: 0.398

Gnomad EAS exome AF: 0.498

Gnomad FIN exome AF: 0.422

Gnomad NFE exome AF: 0.462

Gnomad OTH exome AF: 0.409

GnomAD4 exome AF: 0.449 AC: 653523 AN: 1454720 Hom.: 149485 Cov.: 32 AF XY: 0.444 AC XY: 321371 AN XY: 723740

African (AFR) AF: 0.327 AC: 10894 AN: 33284

American (AMR) AF: 0.381 AC: 16846 AN: 44158

Ashkenazi Jewish (ASJ) AF: 0.403 AC: 10502 AN: 26054

East Asian (EAS) AF: 0.507 AC: 20096 AN: 39614

South Asian (SAS) AF: 0.294 AC: 25199 AN: 85792

European-Finnish (FIN) AF: 0.434 AC: 23112 AN: 53298

Middle Eastern (MID) AF: 0.320 AC: 1827 AN: 5716

European-Non Finnish (NFE) AF: 0.469 AC: 518637 AN: 1106698

Other (OTH) AF: 0.439 AC: 26410 AN: 60106

GnomAD4 genome AF: 0.415 AC: 63021 AN: 152000 Hom.: 13394 Cov.: 31 AF XY: 0.409 AC XY: 30408 AN XY: 74276

African (AFR) AF: 0.332 AC: 13784 AN: 41468

American (AMR) AF: 0.396 AC: 6062 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.414 AC: 1436 AN: 3470

East Asian (EAS) AF: 0.484 AC: 2495 AN: 5154

South Asian (SAS) AF: 0.286 AC: 1378 AN: 4814

European-Finnish (FIN) AF: 0.435 AC: 4586 AN: 10552

Middle Eastern (MID) AF: 0.306 AC: 90 AN: 294

European-Non Finnish (NFE) AF: 0.470 AC: 31936 AN: 67942

Other (OTH) AF: 0.396 AC: 833 AN: 2106

Alfa AF: 0.442 Hom.: 36094

Bravo AF: 0.411

TwinsUK AF: 0.474 AC: 1759

ALSPAC AF: 0.461 AC: 1778

ESP6500AA AF: 0.332 AC: 1260

ESP6500EA AF: 0.472 AC: 3880

ExAC AF: 0.418 AC: 50517

Asia WGS AF: 0.402 AC: 1398 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.094
BayesDel_addAF	Benign	-0.68	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0057	T
Eigen	Benign	0.16
Eigen_PC	Benign	0.13
FATHMM_MKL	Benign	0.71	D
LIST_S2	Benign	0.68	T
MetaRNN	Benign	0.0031	T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	1.6	L
PhyloP100		1.5
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.058
Sift	Benign	0.054	T
Sift4G	Uncertain	0.015	D
Polyphen		0.97	D
Vest4		0.18
MPC		0.24
ClinPred		0.013	T
GERP RS		4.0
Varity_R		0.090
gMVP		0.082
Mutation Taster		=94/6	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

Other links and lift over

dbSNP: rs56030650; hg19: chr17-38131187; COSMIC: COSV56976382; COSMIC: COSV56976382;