Genetic Variant GSDMA:p.Asn6Asn (chr17-39965705-T-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_178171.5(GSDMA):c.18T>C(p.Asn6Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000311 in 1,607,342 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0000066 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

GSDMA
NM_178171.5 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.727

Publications

0 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 -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.56).

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.18T>C	p.Asn6Asn	synonymous	Exon 2 of 12	NP_835465.2	Q96QA5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GSDMA	ENST00000301659.9	TSL:1 MANE Select	c.18T>C	p.Asn6Asn	synonymous	Exon 2 of 12	ENSP00000301659.4	Q96QA5
GSDMA	ENST00000635792.1	TSL:5	c.18T>C	p.Asn6Asn	synonymous	Exon 2 of 12	ENSP00000490739.1	Q96QA5
GSDMA	ENST00000577447.1	TSL:4	c.18T>C	p.Asn6Asn	synonymous	Exon 2 of 4	ENSP00000461985.1	J3KRG2

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

151920

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00

AC:

AN:

238750

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000275

AC:

AN:

1455422

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

AN XY:

723392

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33362

American (AMR)

AF:

0.00

AC:

AN:

43744

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25978

East Asian (EAS)

AF:

0.00

AC:

AN:

39416

South Asian (SAS)

AF:

0.00

AC:

AN:

84850

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52960

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.00000361

AC:

AN:

1109184

Other (OTH)

AF:

0.00

AC:

AN:

60166

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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:

0.00000658

AC:

AN:

151920

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74180

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41364

American (AMR)

AF:

0.00

AC:

AN:

15240

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00

AC:

AN:

4808

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10576

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

67968

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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:

0.0000282

Hom.:

Bravo

AF:

0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.56

CADD

Benign

7.8

(source)

DANN

Benign

0.60

PhyloP100

0.73

PromoterAI

0.11

Neutral

(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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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