Genetic Variant NM_024736.7:c.29G>A (chr8-143559364-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_024736.7(GSDMD):c.29G>A(p.Arg10Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000355 in 1,604,596 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000040 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000035 ( 0 hom. )

Consequence

GSDMD
NM_024736.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.875

Publications

0 publications found

Variant links:

Genes affected

GSDMD (HGNC:25697): (gasdermin D) Gasdermin D is a member of the gasdermin family. Members of this family appear to play a role in regulation of epithelial proliferation. Gasdermin D has been suggested to act as a tumor suppressor. Alternatively spliced transcript variants have been described. [provided by RefSeq, Oct 2009]

GSDMD links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.18258762).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024736.7. 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
	GSDMD	NM_024736.7	MANE Select	c.29G>A	p.Arg10Gln	missense	Exon 2 of 11	NP_079012.3
	GSDMD	NM_001166237.1		c.29G>A	p.Arg10Gln	missense	Exon 5 of 14	NP_001159709.1	P57764

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GSDMD	ENST00000262580.9	TSL:1 MANE Select	c.29G>A	p.Arg10Gln	missense	Exon 2 of 11	ENSP00000262580.4	P57764
GSDMD	ENST00000533063.5	TSL:1	c.173G>A	p.Arg58Gln	missense	Exon 3 of 12	ENSP00000433958.1	G3V1A6
GSDMD	ENST00000526406.5	TSL:2	c.29G>A	p.Arg10Gln	missense	Exon 5 of 14	ENSP00000433209.1	P57764

Frequencies

GnomAD3 genomes

AF:

0.0000400

AC:

AN:

149848

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000491

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000133

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:

0.0000296

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000280

AC:

AN:

249776

AF XY:

0.0000148

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.0000267

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.0000351

AC:

AN:

1454748

Hom.:

Cov.:

AF XY:

0.0000304

AC XY:

AN XY:

723594

show subpopulations

African (AFR)

AF:

0.0000300

AC:

AN:

33278

American (AMR)

AF:

0.0000225

AC:

AN:

44504

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25868

East Asian (EAS)

AF:

0.0000254

AC:

AN:

39344

South Asian (SAS)

AF:

0.00

AC:

AN:

86192

European-Finnish (FIN)

AF:

0.0000770

AC:

AN:

51980

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5724

European-Non Finnish (NFE)

AF:

0.0000379

AC:

AN:

1107936

Other (OTH)

AF:

0.0000334

AC:

AN:

59922

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

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:

0.0000400

AC:

AN:

149848

Hom.:

Cov.:

AF XY:

0.0000411

AC XY:

AN XY:

73050

show subpopulations

African (AFR)

AF:

0.0000491

AC:

AN:

40752

American (AMR)

AF:

0.000133

AC:

AN:

15012

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3438

East Asian (EAS)

AF:

0.00

AC:

AN:

5006

South Asian (SAS)

AF:

0.00

AC:

AN:

4652

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10190

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000296

AC:

AN:

67512

Other (OTH)

AF:

0.00

AC:

AN:

2068

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

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:

0.00

Hom.:

Bravo

AF:

0.0000264

ExAC

AF:

0.0000330

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.088

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.53

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.095

Eigen

Benign

-0.49

Eigen_PC

Benign

-0.69

FATHMM_MKL

Benign

0.013

M_CAP

Benign

0.064

MetaRNN

Benign

0.18

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.8

PhyloP100

-0.88

PrimateAI

Benign

0.28

PROVEAN

Benign

-1.6

REVEL

Benign

0.10

Sift

Benign

0.050

Sift4G

Uncertain

0.033

Polyphen

0.85

Vest4

0.15

MutPred

0.66

Loss of MoRF binding (P = 0.043)

MVP

0.099

MPC

0.41

ClinPred

0.24

GERP RS

-0.69

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.090

gMVP

0.26

Mutation Taster

=90/10

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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