Variant rs56030650 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

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. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.41 ( 13394 hom., cov: 31)

Exomes 𝑓: 0.45 ( 149485 hom. )

Consequence

GSDMA
NM_178171.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.48

Variant links:

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]

GSDMA links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
GSDMA	NM_178171.5 linkuse as main transcript	c.941C>A	p.Thr314Asn	missense_variant	10/12	ENST00000301659.9	NP_835465.2
GSDMA	XM_006721832.4 linkuse as main transcript	c.941C>A	p.Thr314Asn	missense_variant	10/12		XP_006721895.1
GSDMA	XM_017024502.3 linkuse as main transcript	c.914C>A	p.Thr305Asn	missense_variant	9/11		XP_016879991.1
GSDMA	XM_011524651.4 linkuse as main transcript	c.515C>A	p.Thr172Asn	missense_variant	8/10		XP_011522953.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GSDMA	ENST00000301659.9 linkuse as main transcript	c.941C>A	p.Thr314Asn	missense_variant	10/12	1	NM_178171.5	ENSP00000301659	P1
GSDMA	ENST00000635792.1 linkuse as main transcript	c.941C>A	p.Thr314Asn	missense_variant	10/12	5		ENSP00000490739	P1

Frequencies

GnomAD3 genomes

AF:

0.415

AC:

62978

AN:

151882

Hom.:

13385

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.416

AC:

102249

AN:

246038

Hom.:

21717

AF XY:

0.411

AC XY:

54891

AN XY:

133468

show subpopulations

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 SAS exome

AF:

0.289

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.:

AF XY:

0.444

AC XY:

321371

AN XY:

723740

show subpopulations

Gnomad4 AFR exome

AF:

0.327

Gnomad4 AMR exome

AF:

0.381

Gnomad4 ASJ exome

AF:

0.403

Gnomad4 EAS exome

AF:

0.507

Gnomad4 SAS exome

AF:

0.294

Gnomad4 FIN exome

AF:

0.434

Gnomad4 NFE exome

AF:

0.469

Gnomad4 OTH exome

AF:

0.439

GnomAD4 genome

AF:

0.415

AC:

63021

AN:

152000

Hom.:

13394

Cov.:

AF XY:

0.409

AC XY:

30408

AN XY:

74276

show subpopulations

Gnomad4 AFR

AF:

0.332

Gnomad4 AMR

AF:

0.396

Gnomad4 ASJ

AF:

0.414

Gnomad4 EAS

AF:

0.484

Gnomad4 SAS

AF:

0.286

Gnomad4 FIN

AF:

0.435

Gnomad4 NFE

AF:

0.470

Gnomad4 OTH

AF:

0.396

Alfa

AF:

0.449

Hom.:

24959

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 v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.094

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.61

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0057

T;T

Eigen

Benign

0.16

Eigen_PC

Benign

0.13

FATHMM_MKL

Benign

0.71

LIST_S2

Benign

0.68

.;T

MetaRNN

Benign

0.0031

T;T

MetaSVM

Benign

-0.89

MutationAssessor

Benign

1.6

L;L

MutationTaster

Benign

0.62

PrimateAI

Benign

0.43

PROVEAN

Benign

-1.6

.;N

REVEL

Benign

0.058

Sift

Benign

0.054

.;T

Sift4G

Uncertain

0.015

.;D

Polyphen

0.97

D;D

Vest4

0.18

MPC

0.24

ClinPred

0.013

GERP RS

4.0

Varity_R

0.090

gMVP

0.082

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over