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

Variant summary

Our verdict is Benign. The variant received -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

Publications

39 publications found

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

new If you want to explore the variant's impact on the transcript ENST00000635792.1, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000635792.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSDMA	NM_178171.5	MANE Select	c.-90G>T		upstream_gene	N/A	NP_835465.2	Q96QA5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSDMA	ENST00000635792.1	TSL:5	c.-5-2682G>T		intron	N/A	ENSP00000490739.1	Q96QA5
	GSDMA	ENST00000301659.9	TSL:1 MANE Select	c.-90G>T		upstream_gene	N/A	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

African (AFR)

AF:

0.400

AC:

AN:

American (AMR)

AF:

1.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.500

AC:

AN:

East Asian (EAS)

AF:

0.409

AC:

AN:

South Asian (SAS)

AF:

0.591

AC:

AN:

European-Finnish (FIN)

AF:

0.444

AC:

AN:

Middle Eastern (MID)

AF:

0.750

AC:

AN:

European-Non Finnish (NFE)

AF:

0.545

AC:

133

AN:

244

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.557

AC:

84645

AN:

151912

Hom.:

23671

Cov.:

AF XY:

0.556

AC XY:

41259

AN XY:

74234

show subpopulations

African (AFR)

AF:

0.548

AC:

22683

AN:

41394

American (AMR)

AF:

0.563

AC:

8595

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.498

AC:

1728

AN:

3468

East Asian (EAS)

AF:

0.572

AC:

2955

AN:

5168

South Asian (SAS)

AF:

0.514

AC:

2475

AN:

4814

European-Finnish (FIN)

AF:

0.548

AC:

5786

AN:

10552

Middle Eastern (MID)

AF:

0.531

AC:

156

AN:

294

European-Non Finnish (NFE)

AF:

0.569

AC:

38679

AN:

67934

Other (OTH)

AF:

0.541

AC:

1143

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1888

3776

5665

7553

9441

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

734

1468

2202

2936

3670

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.561

Hom.:

103701

Bravo

AF:

0.564

Asia WGS

AF:

0.550

AC:

1914

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

(source)

DANN

Benign

0.63

PhyloP100

0.96

PromoterAI

0.036

Neutral

(source)

Mutation Taster

=300/0

polymorphism (auto)

(source)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over