Variant chr18-30994506-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_001941.5(DSC3):c.2494-134C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0911 in 1,577,370 control chromosomes in the GnomAD database, including 13,397 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.19 ( 5176 hom., cov: 32)

Exomes 𝑓: 0.080 ( 8221 hom. )

Consequence

DSC3
NM_001941.5 intron

Scores

Splicing: ADA: 0.0001368

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 2.07

Variant links:

Genes affected

DSC3 (HGNC:3037): (desmocollin 3) The protein encoded by this gene is a calcium-dependent glycoprotein that is a member of the desmocollin subfamily of the cadherin superfamily. These desmosomal family members, along with the desmogleins, are found primarily in epithelial cells where they constitute the adhesive proteins of the desmosome cell-cell junction and are required for cell adhesion and desmosome formation. The desmosomal family members are arranged in two clusters on chromosome 18, occupying less than 650 kb combined. Mutations in this gene are a cause of hypotrichosis and recurrent skin vesicles disorder. The protein can act as an autoantigen in pemphigus diseases, and it is also considered to be a biomarker for some cancers. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Apr 2014]

DSC3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.31).

BP6

Variant 18-30994506-G-A is Benign according to our data. Variant chr18-30994506-G-A is described in ClinVar as [Benign]. Clinvar id is 1276898.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.462 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DSC3	NM_001941.5 link	c.2494-134C>T		intron_variant		ENST00000360428.9	NP_001932.2	Q14574-1
DSC3	NM_024423.4 link	c.2494-10C>T		intron_variant			NP_077741.2	Q14574-2

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
DSC3	ENST00000360428.9 link	c.2494-134C>T	intron_variant	1	NM_001941.5	ENSP00000353608.4	Q14574-1
DSC3	ENST00000434452.5 link	c.2494-10C>T	intron_variant	5		ENSP00000392068.1	Q14574-2
DSC3	ENST00000584980.1 link	c.616-10C>T	intron_variant	5		ENSP00000464283.1	J3QRL9

Frequencies

GnomAD3 genomes

AF:

0.194

AC:

29412

AN:

151994

Hom.:

5160

Cov.:

show subpopulations

Gnomad AFR

AF:

0.468

Gnomad AMI

AF:

0.116

Gnomad AMR

AF:

0.192

Gnomad ASJ

AF:

0.117

Gnomad EAS

AF:

0.136

Gnomad SAS

AF:

0.139

Gnomad FIN

AF:

0.0217

Gnomad MID

AF:

0.142

Gnomad NFE

AF:

0.0680

Gnomad OTH

AF:

0.174

GnomAD3 exomes

AF:

0.125

AC:

31335

AN:

250608

Hom.:

3540

AF XY:

0.117

AC XY:

15912

AN XY:

135504

show subpopulations

Gnomad AFR exome

AF:

0.482

Gnomad AMR exome

AF:

0.203

Gnomad ASJ exome

AF:

0.111

Gnomad EAS exome

AF:

0.132

Gnomad SAS exome

AF:

0.142

Gnomad FIN exome

AF:

0.0212

Gnomad NFE exome

AF:

0.0664

Gnomad OTH exome

AF:

0.112

GnomAD4 exome

AF:

0.0801

AC:

114225

AN:

1425258

Hom.:

8221

Cov.:

AF XY:

0.0813

AC XY:

57749

AN XY:

710246

show subpopulations

Gnomad4 AFR exome

AF:

0.469

Gnomad4 AMR exome

AF:

0.202

Gnomad4 ASJ exome

AF:

0.110

Gnomad4 EAS exome

AF:

0.115

Gnomad4 SAS exome

AF:

0.134

Gnomad4 FIN exome

AF:

0.0241

Gnomad4 NFE exome

AF:

0.0591

Gnomad4 OTH exome

AF:

0.103

GnomAD4 genome

AF:

0.194

AC:

29475

AN:

152112

Hom.:

5176

Cov.:

AF XY:

0.189

AC XY:

14022

AN XY:

74380

show subpopulations

Gnomad4 AFR

AF:

0.468

Gnomad4 AMR

AF:

0.192

Gnomad4 ASJ

AF:

0.117

Gnomad4 EAS

AF:

0.137

Gnomad4 SAS

AF:

0.140

Gnomad4 FIN

AF:

0.0217

Gnomad4 NFE

AF:

0.0680

Gnomad4 OTH

AF:

0.175

Alfa

AF:

0.120

Hom.:

1370

Bravo

AF:

0.220

Asia WGS

AF:

0.161

AC:

560

AN:

3472

ClinVar

Significance: Benign

Submissions summary: Benign:3

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	GeneDx	Nov 11, 2018	- -

DSC3-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 04, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.31

CADD

Benign

DANN

Benign

0.72

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00014

dbscSNV1_RF

Benign

0.076

SpliceAI score (max)

0.11

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