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18-30996827-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_001941.5(DSC3):c.2457G>A(p.Ser819=) 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

2

Clinical Significance

Benign criteria provided, single submitter B:1

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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.62).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
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_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-4.81 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
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 UniProt
DSC3NM_001941.5 linkuse as main transcriptc.2457G>A p.Ser819= synonymous_variant 15/16 ENST00000360428.9
DSC3NM_024423.4 linkuse as main transcriptc.2457G>A p.Ser819= synonymous_variant 15/17

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
DSC3ENST00000360428.9 linkuse as main transcriptc.2457G>A p.Ser819= synonymous_variant 15/161 NM_001941.5 P1Q14574-1
DSC3ENST00000434452.5 linkuse as main transcriptc.2457G>A p.Ser819= synonymous_variant 15/175 Q14574-2
DSC3ENST00000584980.1 linkuse as main transcriptc.582G>A p.Ser194= synonymous_variant 4/65

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0320
AC:
4852
AN:
151736
Hom.:
286
Cov.:
32
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.:
31
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
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0320
AC:
4860
AN:
151854
Hom.:
288
Cov.:
32
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.:
46
Bravo
AF:
0.0375
Asia WGS
AF:
0.00549
AC:
19
AN:
3478
EpiCase
AF:
0.000109
EpiControl
AF:
0.000237

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 submitterclinical testingGeneDxNov 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.

Other links and lift over

dbSNP: rs2228474; hg19: chr18-28576793; COSMIC: COSV64573221; API