Variant 8-143560611-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_024736.7(GSDMD):c.419G>A(p.Arg140Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000265 in 1,583,082 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R140L) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 34)

Exomes 𝑓: 0.000027 ( 0 hom. )

Consequence

GSDMD
NM_024736.7 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.166

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 made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.029907674).

BP6

Variant 8-143560611-G-A is Benign according to our data. Variant chr8-143560611-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3102818.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GSDMD	NM_024736.7 linkuse as main transcript	c.419G>A	p.Arg140Gln	missense_variant	4/11	ENST00000262580.9
GSDMD	NM_001166237.1 linkuse as main transcript	c.419G>A	p.Arg140Gln	missense_variant	7/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GSDMD	ENST00000262580.9 linkuse as main transcript	c.419G>A	p.Arg140Gln	missense_variant	4/11	1	NM_024736.7	P2

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152234

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000578

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000150

AC:

AN:

199644

Hom.:

AF XY:

0.0000275

AC XY:

AN XY:

109012

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000676

Gnomad SAS exome

AF:

0.0000768

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000266

AC:

AN:

1430730

Hom.:

Cov.:

AF XY:

0.0000324

AC XY:

AN XY:

709070

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000555

Gnomad4 SAS exome

AF:

0.0000607

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000109

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152352

Hom.:

Cov.:

AF XY:

0.0000537

AC XY:

AN XY:

74504

show subpopulations

Gnomad4 AFR

AF:

0.0000240

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000579

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ExAC

AF:

0.0000168

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 02, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.082

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.60

CADD

Benign

DANN

Benign

0.86

DEOGEN2

Benign

0.062

T;.;.;T;.;T

Eigen

Benign

-0.99

Eigen_PC

Benign

-0.91

FATHMM_MKL

Benign

0.26

M_CAP

Benign

0.022

MetaRNN

Benign

0.030

T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.28

N;.;.;N;.;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.23

PROVEAN

Benign

-1.6

N;N;N;N;N;N

REVEL

Benign

0.052

Sift

Benign

0.52

T;T;T;T;T;T

Sift4G

Benign

0.49

T;T;T;T;T;T

Polyphen

0.39

B;.;B;B;.;.

Vest4

0.16

MVP

0.12

MPC

0.17

ClinPred

0.034

GERP RS

1.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.13

gMVP

0.15

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over