Variant 7-24702817-T-C 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_001127453.2(GSDME):c.1200A>G(p.Ala400=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.166 in 1,612,490 control chromosomes in the GnomAD database, including 24,394 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.17 ( 2310 hom., cov: 33)

Exomes 𝑓: 0.17 ( 22084 hom. )

Consequence

GSDME
NM_001127453.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.285

Variant links:

Genes affected

GSDME (HGNC:2810): (gasdermin E) Hearing impairment is a heterogeneous condition with over 40 loci described. The protein encoded by this gene is expressed in fetal cochlea, however, its function is not known. Nonsyndromic hearing impairment is associated with a mutation in this gene. Three transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

GSDME links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 7-24702817-T-C is Benign according to our data. Variant chr7-24702817-T-C is described in ClinVar as [Benign]. Clinvar id is 44840.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.285 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.255 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GSDME	NM_001127453.2 linkuse as main transcript	c.1200A>G	p.Ala400=	synonymous_variant	9/10	ENST00000645220.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GSDME	ENST00000645220.1 linkuse as main transcript	c.1200A>G	p.Ala400=	synonymous_variant	9/10		NM_001127453.2	P1	O60443-1

Frequencies

GnomAD3 genomes

AF:

0.168

AC:

25534

AN:

152104

Hom.:

2312

Cov.:

show subpopulations

Gnomad AFR

AF:

0.126

Gnomad AMI

AF:

0.0593

Gnomad AMR

AF:

0.254

Gnomad ASJ

AF:

0.185

Gnomad EAS

AF:

0.267

Gnomad SAS

AF:

0.231

Gnomad FIN

AF:

0.212

Gnomad MID

AF:

0.241

Gnomad NFE

AF:

0.155

Gnomad OTH

AF:

0.174

GnomAD3 exomes

AF:

0.201

AC:

50594

AN:

251402

Hom.:

5793

AF XY:

0.197

AC XY:

26822

AN XY:

135878

show subpopulations

Gnomad AFR exome

AF:

0.129

Gnomad AMR exome

AF:

0.324

Gnomad ASJ exome

AF:

0.188

Gnomad EAS exome

AF:

0.278

Gnomad SAS exome

AF:

0.227

Gnomad FIN exome

AF:

0.205

Gnomad NFE exome

AF:

0.155

Gnomad OTH exome

AF:

0.201

GnomAD4 exome

AF:

0.166

AC:

242933

AN:

1460268

Hom.:

22084

Cov.:

AF XY:

0.169

AC XY:

122671

AN XY:

726456

show subpopulations

Gnomad4 AFR exome

AF:

0.128

Gnomad4 AMR exome

AF:

0.314

Gnomad4 ASJ exome

AF:

0.184

Gnomad4 EAS exome

AF:

0.289

Gnomad4 SAS exome

AF:

0.230

Gnomad4 FIN exome

AF:

0.206

Gnomad4 NFE exome

AF:

0.149

Gnomad4 OTH exome

AF:

0.175

GnomAD4 genome

AF:

0.168

AC:

25539

AN:

152222

Hom.:

2310

Cov.:

AF XY:

0.176

AC XY:

13098

AN XY:

74416

show subpopulations

Gnomad4 AFR

AF:

0.126

Gnomad4 AMR

AF:

0.254

Gnomad4 ASJ

AF:

0.185

Gnomad4 EAS

AF:

0.267

Gnomad4 SAS

AF:

0.233

Gnomad4 FIN

AF:

0.212

Gnomad4 NFE

AF:

0.155

Gnomad4 OTH

AF:

0.172

Alfa

AF:

0.148

Hom.:

3075

Bravo

AF:

0.169

Asia WGS

AF:

0.253

AC:

878

AN:

3478

EpiCase

AF:

0.160

EpiControl

AF:

0.157

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 09, 2017	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	May 07, 2012	Ala400Ala in Exon 09 of DFNA5: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue, is not located withi n the splice consensus sequence, and has been identified in 15.6% (1098/7020) of European American chromosomes from a broad population by the NHLBI Exome Sequen cing Project (http://evs.gs.washington.edu/EVS; dbSNP rs17149912). -

Autosomal dominant nonsyndromic hearing loss 5

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

4.8

DANN

Benign

0.42

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