Variant 18-30994547-AG-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_001941.5(DSC3):c.2494-176delC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0407 in 1,422,866 control chromosomes in the GnomAD database, including 1,468 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.035 ( 148 hom., cov: 32)

Exomes 𝑓: 0.041 ( 1320 hom. )

Consequence

DSC3
NM_001941.5 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.499

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP6

Variant 18-30994547-AG-A is Benign according to our data. Variant chr18-30994547-AG-A is described in ClinVar as [Benign]. Clinvar id is 1287128.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0543 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DSC3	NM_001941.5 link	c.2494-176delC		intron_variant		ENST00000360428.9	NP_001932.2	Q14574-1
DSC3	NM_024423.4 link	c.2494-52delC		intron_variant			NP_077741.2	Q14574-2

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
DSC3	ENST00000360428.9 link	c.2494-176delC	intron_variant	1	NM_001941.5	ENSP00000353608.4	Q14574-1
DSC3	ENST00000434452.5 link	c.2494-52delC	intron_variant	5		ENSP00000392068.1	Q14574-2
DSC3	ENST00000584980.1 link	c.616-52delC	intron_variant	5		ENSP00000464283.1	J3QRL9

Frequencies

GnomAD3 genomes

AF:

0.0348

AC:

5290

AN:

152204

Hom.:

149

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0168

Gnomad AMI

AF:

0.0132

Gnomad AMR

AF:

0.0263

Gnomad ASJ

AF:

0.0256

Gnomad EAS

AF:

0.000769

Gnomad SAS

AF:

0.0496

Gnomad FIN

AF:

0.0630

Gnomad MID

AF:

0.0665

Gnomad NFE

AF:

0.0454

Gnomad OTH

AF:

0.0344

GnomAD3 exomes

AF:

0.0374

AC:

9283

AN:

247992

Hom.:

260

AF XY:

0.0399

AC XY:

5341

AN XY:

133946

show subpopulations

Gnomad AFR exome

AF:

0.0173

Gnomad AMR exome

AF:

0.0198

Gnomad ASJ exome

AF:

0.0284

Gnomad EAS exome

AF:

0.000110

Gnomad SAS exome

AF:

0.0535

Gnomad FIN exome

AF:

0.0632

Gnomad NFE exome

AF:

0.0431

Gnomad OTH exome

AF:

0.0419

GnomAD4 exome

AF:

0.0414

AC:

52638

AN:

1270544

Hom.:

1320

Cov.:

AF XY:

0.0422

AC XY:

27015

AN XY:

640192

show subpopulations

Gnomad4 AFR exome

AF:

0.0171

Gnomad4 AMR exome

AF:

0.0200

Gnomad4 ASJ exome

AF:

0.0262

Gnomad4 EAS exome

AF:

0.000142

Gnomad4 SAS exome

AF:

0.0551

Gnomad4 FIN exome

AF:

0.0626

Gnomad4 NFE exome

AF:

0.0428

Gnomad4 OTH exome

AF:

0.0406

GnomAD4 genome

AF:

0.0347

AC:

5288

AN:

152322

Hom.:

148

Cov.:

AF XY:

0.0364

AC XY:

2713

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.0168

Gnomad4 AMR

AF:

0.0263

Gnomad4 ASJ

AF:

0.0256

Gnomad4 EAS

AF:

0.000771

Gnomad4 SAS

AF:

0.0501

Gnomad4 FIN

AF:

0.0630

Gnomad4 NFE

AF:

0.0454

Gnomad4 OTH

AF:

0.0331

Alfa

AF:

0.0312

Hom.:

Bravo

AF:

0.0295

Asia WGS

AF:

0.0170

AC:

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 20, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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