Genetic Variant NM_178171.5:c.558+36_558+37dupAC (chr17-39970658-A-AAC) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_178171.5(GSDMA):c.558+36_558+37dupAC variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0040 ( 2 hom., cov: 0)

Exomes 𝑓: 0.0060 ( 2 hom. )

Consequence

GSDMA
NM_178171.5 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.827

Publications

2 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

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSDMA	NM_178171.5	MANE Select	c.558+36_558+37dupAC		intron	N/A	NP_835465.2	Q96QA5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
GSDMA	ENST00000301659.9	TSL:1 MANE Select	c.558+11_558+12insAC	intron	N/A	ENSP00000301659.4	Q96QA5
GSDMA	ENST00000635792.1	TSL:5	c.558+11_558+12insAC	intron	N/A	ENSP00000490739.1	Q96QA5
GSDMA	ENST00000577447.1	TSL:4	c.93_94insAC	downstream_gene	N/A	ENSP00000461985.1	J3KRG2

Frequencies

GnomAD3 genomes

AF:

0.00396

AC:

596

AN:

150608

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00478

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00165

Gnomad ASJ

AF:

0.00174

Gnomad EAS

AF:

0.000787

Gnomad SAS

AF:

0.00190

Gnomad FIN

AF:

0.000385

Gnomad MID

AF:

0.00323

Gnomad NFE

AF:

0.00514

Gnomad OTH

AF:

0.00194

GnomAD2 exomes

AF:

0.00305

AC:

158

AN:

51756

AF XY:

0.00284

show subpopulations

Gnomad AFR exome

AF:

0.00437

Gnomad AMR exome

AF:

0.00241

Gnomad ASJ exome

AF:

0.00281

Gnomad EAS exome

AF:

0.000638

Gnomad FIN exome

AF:

0.000953

Gnomad NFE exome

AF:

0.00466

Gnomad OTH exome

AF:

0.00303

GnomAD4 exome

AF:

0.00596

AC:

7159

AN:

1201914

Hom.:

Cov.:

AF XY:

0.00578

AC XY:

3383

AN XY:

585382

show subpopulations

African (AFR)

AF:

0.00440

AC:

113

AN:

25672

American (AMR)

AF:

0.00200

AC:

AN:

17506

Ashkenazi Jewish (ASJ)

AF:

0.00209

AC:

AN:

17704

East Asian (EAS)

AF:

0.000451

AC:

AN:

28798

South Asian (SAS)

AF:

0.00141

AC:

AN:

56546

European-Finnish (FIN)

AF:

0.000961

AC:

AN:

42648

Middle Eastern (MID)

AF:

0.00193

AC:

AN:

3630

European-Non Finnish (NFE)

AF:

0.00694

AC:

6662

AN:

960314

Other (OTH)

AF:

0.00348

AC:

171

AN:

49096

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.410

Heterozygous variant carriers

316

632

948

1264

1580

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

290

580

870

1160

1450

<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:

0.00395

AC:

596

AN:

150730

Hom.:

Cov.:

AF XY:

0.00352

AC XY:

259

AN XY:

73562

show subpopulations

African (AFR)

AF:

0.00477

AC:

196

AN:

41100

American (AMR)

AF:

0.00165

AC:

AN:

15178

Ashkenazi Jewish (ASJ)

AF:

0.00174

AC:

AN:

3448

East Asian (EAS)

AF:

0.000789

AC:

AN:

5070

South Asian (SAS)

AF:

0.00190

AC:

AN:

4742

European-Finnish (FIN)

AF:

0.000385

AC:

AN:

10402

Middle Eastern (MID)

AF:

0.00345

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.00514

AC:

347

AN:

67518

Other (OTH)

AF:

0.00192

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

120

150

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome 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

Alfa

AF:

0.00211

Hom.:

981

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.83

Mutation Taster

=100/0

polymorphism

(source)

Splicing

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