Variant 8-143559344-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_024736.7(GSDMD):c.9G>T(p.Ser3Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00506 in 1,610,978 control chromosomes in the GnomAD database, including 311 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.026 ( 163 hom., cov: 31)

Exomes 𝑓: 0.0029 ( 148 hom. )

Consequence

GSDMD
NM_024736.7 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -8.62

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:

GSDMD (HGNC:):

GSDMD links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.02).

BP6

Variant 8-143559344-G-T is Benign according to our data. Variant chr8-143559344-G-T is described in ClinVar as [Benign]. Clinvar id is 781163.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-8.62 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0861 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GSDMD	NM_024736.7 linkuse as main transcript	c.9G>T	p.Ser3Ser	synonymous_variant	2/11	ENST00000262580.9	NP_079012.3	P57764
GSDMD	NM_001166237.1 linkuse as main transcript	c.9G>T	p.Ser3Ser	synonymous_variant	5/14		NP_001159709.1	P57764

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GSDMD	ENST00000262580.9 linkuse as main transcript	c.9G>T	p.Ser3Ser	synonymous_variant	2/11	1	NM_024736.7	ENSP00000262580.4		P57764

Frequencies

GnomAD3 genomes

AF:

0.0258

AC:

3905

AN:

151160

Hom.:

163

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0887

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0129

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000625

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000309

Gnomad OTH

AF:

0.0235

GnomAD3 exomes

AF:

0.00723

AC:

1798

AN:

248748

Hom.:

AF XY:

0.00532

AC XY:

718

AN XY:

135072

show subpopulations

Gnomad AFR exome

AF:

0.0945

Gnomad AMR exome

AF:

0.00563

Gnomad ASJ exome

AF:

0.000101

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000655

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000393

Gnomad OTH exome

AF:

0.00709

GnomAD4 exome

AF:

0.00291

AC:

4246

AN:

1459710

Hom.:

148

Cov.:

AF XY:

0.00253

AC XY:

1834

AN XY:

726078

show subpopulations

Gnomad4 AFR exome

AF:

0.0927

Gnomad4 AMR exome

AF:

0.00719

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000162

Gnomad4 FIN exome

AF:

0.0000192

Gnomad4 NFE exome

AF:

0.000361

Gnomad4 OTH exome

AF:

0.00626

GnomAD4 genome

AF:

0.0258

AC:

3909

AN:

151268

Hom.:

163

Cov.:

AF XY:

0.0246

AC XY:

1819

AN XY:

73898

show subpopulations

Gnomad4 AFR

AF:

0.0885

Gnomad4 AMR

AF:

0.0128

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000626

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000309

Gnomad4 OTH

AF:

0.0233

Alfa

AF:

0.00779

Hom.:

Bravo

AF:

0.0309

Asia WGS

AF:

0.00375

AC:

AN:

3478

EpiCase

AF:

0.000709

EpiControl

AF:

0.000533

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Apr 04, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.0050

DANN

Benign

0.37

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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

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