rs3894194

Variant names:

• chr17-39965740-G-A
• rs3894194
• NM_178171.5:c.53G>A

Your query was ambiguous. Multiple possible variants found:

• chr17-39965740-G-A
• chr17-39965740-G-C
• chr17-39965740-G-T

Variant summary

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

The NM_178171.5(GSDMA):​c.53G>A​(p.Arg18Gln) 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 1,609,784 control chromosomes in the GnomAD database, including 162,085 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 (13320 hom., cov: 30)
  • Exomes 𝑓: 0.45 (148765 hom.)
• Consequence: GSDMA NM_178171.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.01
• Publications: 125 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=3.8951635E-4).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.536 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GSDMA	NM_178171.5	c.53G>A	p.Arg18Gln	missense_variant	Exon 2 of 12	ENST00000301659.9	NP_835465.2
GSDMA	XM_006721832.4	c.53G>A	p.Arg18Gln	missense_variant	Exon 2 of 12		XP_006721895.1
GSDMA	XM_017024502.3	c.53G>A	p.Arg18Gln	missense_variant	Exon 2 of 11		XP_016879991.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GSDMA	ENST00000301659.9	c.53G>A	p.Arg18Gln	missense_variant	Exon 2 of 12	1	NM_178171.5	ENSP00000301659.4
GSDMA	ENST00000635792.1	c.53G>A	p.Arg18Gln	missense_variant	Exon 2 of 12	5		ENSP00000490739.1
GSDMA	ENST00000577447.1	c.53G>A	p.Arg18Gln	missense_variant	Exon 2 of 4	4		ENSP00000461985.1

Frequencies

GnomAD3 genomes AF: 0.413 AC: 62613 AN: 151754 Hom.: 13327 Cov.: 30

Gnomad AFR AF: 0.302

Gnomad AMI AF: 0.448

Gnomad AMR AF: 0.467

Gnomad ASJ AF: 0.396

Gnomad EAS AF: 0.552

Gnomad SAS AF: 0.445

Gnomad FIN AF: 0.398

Gnomad MID AF: 0.386

Gnomad NFE AF: 0.458

Gnomad OTH AF: 0.411

GnomAD2 exomes AF: 0.458 AC: 111394 AN: 243136 AF XY: 0.455

Gnomad AFR exome AF: 0.291

Gnomad AMR exome AF: 0.574

Gnomad ASJ exome AF: 0.390

Gnomad EAS exome AF: 0.562

Gnomad FIN exome AF: 0.391

Gnomad NFE exome AF: 0.450

Gnomad OTH exome AF: 0.448

GnomAD4 exome AF: 0.450 AC: 655883 AN: 1457912 Hom.: 148765 Cov.: 47 AF XY: 0.450 AC XY: 326090 AN XY: 724894

African (AFR) AF: 0.290 AC: 9695 AN: 33410

American (AMR) AF: 0.561 AC: 24761 AN: 44146

Ashkenazi Jewish (ASJ) AF: 0.395 AC: 10298 AN: 26072

East Asian (EAS) AF: 0.542 AC: 21417 AN: 39498

South Asian (SAS) AF: 0.456 AC: 38990 AN: 85590

European-Finnish (FIN) AF: 0.400 AC: 21244 AN: 53116

Middle Eastern (MID) AF: 0.380 AC: 2190 AN: 5764

European-Non Finnish (NFE) AF: 0.451 AC: 500419 AN: 1110044

Other (OTH) AF: 0.446 AC: 26869 AN: 60272

GnomAD4 genome AF: 0.412 AC: 62610 AN: 151872 Hom.: 13320 Cov.: 30 AF XY: 0.411 AC XY: 30504 AN XY: 74216

African (AFR) AF: 0.301 AC: 12483 AN: 41430

American (AMR) AF: 0.466 AC: 7104 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.396 AC: 1375 AN: 3468

East Asian (EAS) AF: 0.553 AC: 2848 AN: 5152

South Asian (SAS) AF: 0.445 AC: 2137 AN: 4802

European-Finnish (FIN) AF: 0.398 AC: 4202 AN: 10552

Middle Eastern (MID) AF: 0.388 AC: 114 AN: 294

European-Non Finnish (NFE) AF: 0.458 AC: 31073 AN: 67900

Other (OTH) AF: 0.411 AC: 866 AN: 2106

Alfa AF: 0.442 Hom.: 43819

Bravo AF: 0.419

TwinsUK AF: 0.448 AC: 1661

ALSPAC AF: 0.441 AC: 1700

ESP6500AA AF: 0.295 AC: 1170

ESP6500EA AF: 0.456 AC: 3796

ExAC AF: 0.453 AC: 54715

Asia WGS AF: 0.456 AC: 1586 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_addAF	Benign	-0.62	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0054	T;T;T
Eigen	Benign	-0.42
Eigen_PC	Benign	-0.31
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.76	.;T;T
MetaRNN	Benign	0.00039	T;T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.90	L;L;.
PhyloP100		1.0
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-0.99	.;N;.
REVEL	Benign	0.026
Sift	Benign	0.19	.;T;.
Sift4G	Benign	0.22	.;T;T
Polyphen		0.016	B;B;.
Vest4		0.14
MPC		0.092
ClinPred		0.0051	T
GERP RS		3.3
PromoterAI		0.0066	Neutral
Varity_R		0.072
gMVP		0.25
Mutation Taster		=96/4	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs3894194; hg19: chr17-38121993; COSMIC: COSV56978411;