Variant 18-30996827-C-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_001941.5(DSC3):c.2457G>A(p.Ser819Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00606 in 1,613,672 control chromosomes in the GnomAD database, including 530 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.032 ( 288 hom., cov: 32)

Exomes 𝑓: 0.0034 ( 242 hom. )

Consequence

DSC3
NM_001941.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -4.81

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.62).

BP6

Variant 18-30996827-C-T is Benign according to our data. Variant chr18-30996827-C-T is described in ClinVar as [Benign]. Clinvar id is 1267408.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-4.81 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.109 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DSC3	NM_001941.5 link	c.2457G>A	p.Ser819Ser	synonymous_variant	15/16	ENST00000360428.9	NP_001932.2	Q14574-1
DSC3	NM_024423.4 link	c.2457G>A	p.Ser819Ser	synonymous_variant	15/17		NP_077741.2	Q14574-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
DSC3	ENST00000360428.9 link	c.2457G>A	p.Ser819Ser	synonymous_variant	15/16	1	NM_001941.5	ENSP00000353608.4	Q14574-1
DSC3	ENST00000434452.5 link	c.2457G>A	p.Ser819Ser	synonymous_variant	15/17	5		ENSP00000392068.1	Q14574-2
DSC3	ENST00000584980.1 link	c.579G>A	p.Ser193Ser	synonymous_variant	4/6	5		ENSP00000464283.1	J3QRL9

Frequencies

GnomAD3 genomes

AF:

0.0320

AC:

4852

AN:

151736

Hom.:

286

Cov.:

show subpopulations

Gnomad AFR

AF:

0.112

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0117

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.000189

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000368

Gnomad OTH

AF:

0.0231

GnomAD3 exomes

AF:

0.00847

AC:

2127

AN:

251234

Hom.:

137

AF XY:

0.00615

AC XY:

835

AN XY:

135800

show subpopulations

Gnomad AFR exome

AF:

0.115

Gnomad AMR exome

AF:

0.00477

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.000719

Gnomad FIN exome

AF:

0.000277

Gnomad NFE exome

AF:

0.000352

Gnomad OTH exome

AF:

0.00408

GnomAD4 exome

AF:

0.00336

AC:

4915

AN:

1461818

Hom.:

242

Cov.:

AF XY:

0.00292

AC XY:

2127

AN XY:

727220

show subpopulations

Gnomad4 AFR exome

AF:

0.113

Gnomad4 AMR exome

AF:

0.00563

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000649

Gnomad4 FIN exome

AF:

0.000318

Gnomad4 NFE exome

AF:

0.000255

Gnomad4 OTH exome

AF:

0.00780

GnomAD4 genome

AF:

0.0320

AC:

4860

AN:

151854

Hom.:

288

Cov.:

AF XY:

0.0312

AC XY:

2319

AN XY:

74220

show subpopulations

Gnomad4 AFR

AF:

0.111

Gnomad4 AMR

AF:

0.0116

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000209

Gnomad4 FIN

AF:

0.000189

Gnomad4 NFE

AF:

0.000368

Gnomad4 OTH

AF:

0.0228

Alfa

AF:

0.0128

Hom.:

Bravo

AF:

0.0375

Asia WGS

AF:

0.00549

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.000237

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	GeneDx	Nov 11, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

CADD

Benign

0.35

DANN

Benign

0.71

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