Genetic Variant GSDMA:c.-5-2682G>T (chr17-39963001-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000635792.1(GSDMA):c.-5-2682G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.557 in 152,266 control chromosomes in the GnomAD database, including 23,721 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.56 ( 23671 hom., cov: 30)

Exomes 𝑓: 0.53 ( 50 hom. )

Consequence

GSDMA
ENST00000635792.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.964

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 (BayesDel_noAF=-0.81).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.565 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GSDMA	NM_178171.5 link	c.-90G>T		upstream_gene_variant		ENST00000301659.9	NP_835465.2	Q96QA5
GSDMA	XM_017024502.3 link	c.-90G>T		upstream_gene_variant			XP_016879991.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GSDMA	ENST00000635792.1 link	c.-5-2682G>T		intron_variant	Intron 1 of 11	5		ENSP00000490739.1		Q96QA5
GSDMA	ENST00000301659.9 link	c.-90G>T		upstream_gene_variant		1	NM_178171.5	ENSP00000301659.4		Q96QA5

Frequencies

GnomAD3 genomes

AF:

0.557

AC:

84590

AN:

151794

Hom.:

23651

Cov.:

show subpopulations

Gnomad AFR

AF:

0.548

Gnomad AMI

AF:

0.488

Gnomad AMR

AF:

0.564

Gnomad ASJ

AF:

0.498

Gnomad EAS

AF:

0.571

Gnomad SAS

AF:

0.514

Gnomad FIN

AF:

0.548

Gnomad MID

AF:

0.532

Gnomad NFE

AF:

0.569

Gnomad OTH

AF:

0.540

GnomAD4 exome

AF:

0.525

AC:

186

AN:

354

Hom.:

Cov.:

AF XY:

0.550

AC XY:

142

AN XY:

258

show subpopulations

Gnomad4 AFR exome

AF:

0.400

Gnomad4 AMR exome

AF:

1.00

Gnomad4 ASJ exome

AF:

0.500

Gnomad4 EAS exome

AF:

0.409

Gnomad4 SAS exome

AF:

0.591

Gnomad4 FIN exome

AF:

0.444

Gnomad4 NFE exome

AF:

0.545

Gnomad4 OTH exome

AF:

0.500

GnomAD4 genome

AF:

0.557

AC:

84645

AN:

151912

Hom.:

23671

Cov.:

AF XY:

0.556

AC XY:

41259

AN XY:

74234

show subpopulations

Gnomad4 AFR

AF:

0.548

Gnomad4 AMR

AF:

0.563

Gnomad4 ASJ

AF:

0.498

Gnomad4 EAS

AF:

0.572

Gnomad4 SAS

AF:

0.514

Gnomad4 FIN

AF:

0.548

Gnomad4 NFE

AF:

0.569

Gnomad4 OTH

AF:

0.541

Alfa

AF:

0.558

Hom.:

47397

Bravo

AF:

0.564

Asia WGS

AF:

0.550

AC:

1914

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

DANN

Benign

0.63

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