chr18-30996827-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -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

Publications

2 publications found

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 Gene-Disease associations (from GenCC):

hereditary hypotrichosis with recurrent skin vesicles
Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Genomics England PanelApp, PanelApp Australia, G2P, Orphanet, Labcorp Genetics (formerly Invitae)

DSC3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
DSC3	NM_001941.5 link	c.2457G>A	p.Ser819Ser	synonymous_variant	Exon 15 of 16	ENST00000360428.9	NP_001932.2	Q14574-1
DSC3	NM_024423.4 link	c.2457G>A	p.Ser819Ser	synonymous_variant	Exon 15 of 17		NP_077741.2	Q14574-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
DSC3	ENST00000360428.9 link	c.2457G>A	p.Ser819Ser	synonymous_variant	Exon 15 of 16	1	NM_001941.5	ENSP00000353608.4	Q14574-1
DSC3	ENST00000434452.5 link	c.2457G>A	p.Ser819Ser	synonymous_variant	Exon 15 of 17	5		ENSP00000392068.1	Q14574-2
DSC3	ENST00000584980.1 link	c.579G>A	p.Ser193Ser	synonymous_variant	Exon 4 of 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

GnomAD2 exomes

AF:

0.00847

AC:

2127

AN:

251234

AF XY:

0.00615

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 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

African (AFR)

AF:

0.113

AC:

3786

AN:

33478

American (AMR)

AF:

0.00563

AC:

252

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39700

South Asian (SAS)

AF:

0.000649

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.000318

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00837

AC:

AN:

5736

European-Non Finnish (NFE)

AF:

0.000255

AC:

284

AN:

1111980

Other (OTH)

AF:

0.00780

AC:

471

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

242

485

727

970

1212

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

130

260

390

520

650

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0320

AC:

4860

AN:

151854

Hom.:

288

Cov.:

AF XY:

0.0312

AC XY:

2319

AN XY:

74220

show subpopulations

African (AFR)

AF:

0.111

AC:

4603

AN:

41318

American (AMR)

AF:

0.0116

AC:

177

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5146

South Asian (SAS)

AF:

0.000209

AC:

AN:

4796

European-Finnish (FIN)

AF:

0.000189

AC:

AN:

10574

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000368

AC:

AN:

67982

Other (OTH)

AF:

0.0228

AC:

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

209

419

628

838

1047

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

112

168

224

280

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0129

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

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Nov 11, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

CADD

Benign

0.35

(source)

DANN

Benign

0.71

PhyloP100

-4.8

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over