18-30994486-C-G
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_001941.5(DSC3):c.2494-114G>C variant causes a intron change. The variant allele was found at a frequency of 0.00000278 in 1,439,942 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000028 ( 0 hom. )
Consequence
DSC3
NM_001941.5 intron
NM_001941.5 intron
Scores
5
10
Clinical Significance
Conservation
PhyloP100: 3.78
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 Uncertain_significance. Variant got 1 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.4156546).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DSC3 | NM_001941.5 | c.2494-114G>C | intron_variant | ENST00000360428.9 | |||
DSC3 | NM_024423.4 | c.2504G>C | p.Arg835Thr | missense_variant | 16/17 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DSC3 | ENST00000360428.9 | c.2494-114G>C | intron_variant | 1 | NM_001941.5 | P1 | |||
DSC3 | ENST00000434452.5 | c.2504G>C | p.Arg835Thr | missense_variant | 16/17 | 5 | |||
DSC3 | ENST00000584980.1 | c.629G>C | p.Arg210Thr | missense_variant | 5/6 | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome AF: 0.00000278 AC: 4AN: 1439942Hom.: 0 Cov.: 28 AF XY: 0.00000139 AC XY: 1AN XY: 716920
GnomAD4 exome
AF:
AC:
4
AN:
1439942
Hom.:
Cov.:
28
AF XY:
AC XY:
1
AN XY:
716920
Gnomad4 AFR exome
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GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 13, 2023 | The c.2504G>C (p.R835T) alteration is located in exon 16 (coding exon 16) of the DSC3 gene. This alteration results from a G to C substitution at nucleotide position 2504, causing the arginine (R) at amino acid position 835 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Benign
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D
M_CAP
Benign
D
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationTaster
Benign
D;N
PROVEAN
Benign
N
REVEL
Benign
Sift
Uncertain
D
Sift4G
Benign
T
Polyphen
D
Vest4
MutPred
Gain of glycosylation at R835 (P = 0.0258);
MVP
ClinPred
T
GERP RS
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.