chr18-31001635-G-A
Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2
The NM_001941.5(DSC3):c.2218C>T(p.Pro740Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00319 in 1,610,450 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.0023 ( 2 hom., cov: 32)
Exomes 𝑓: 0.0033 ( 8 hom. )
Consequence
DSC3
NM_001941.5 missense
NM_001941.5 missense
Scores
8
4
7
Clinical Significance
Conservation
PhyloP100: 6.52
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 -10 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.014158905).
BP6
?
Variant 18-31001635-G-A is Benign according to our data. Variant chr18-31001635-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3033281.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr18-31001635-G-A is described in Lovd as [Likely_benign].
BS2
?
High Homozygotes in GnomAd at 2 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DSC3 | NM_001941.5 | c.2218C>T | p.Pro740Ser | missense_variant | 14/16 | ENST00000360428.9 | |
DSC3 | NM_024423.4 | c.2218C>T | p.Pro740Ser | missense_variant | 14/17 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DSC3 | ENST00000360428.9 | c.2218C>T | p.Pro740Ser | missense_variant | 14/16 | 1 | NM_001941.5 | P1 | |
DSC3 | ENST00000434452.5 | c.2218C>T | p.Pro740Ser | missense_variant | 14/17 | 5 | |||
DSC3 | ENST00000584980.1 | c.343C>T | p.Pro115Ser | missense_variant | 3/6 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.00233 AC: 355AN: 152034Hom.: 2 Cov.: 32
GnomAD3 genomes
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GnomAD3 exomes AF: 0.00236 AC: 593AN: 250834Hom.: 2 AF XY: 0.00250 AC XY: 339AN XY: 135578
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GnomAD4 exome AF: 0.00328 AC: 4776AN: 1458298Hom.: 8 Cov.: 30 AF XY: 0.00312 AC XY: 2264AN XY: 725384
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GnomAD4 genome ? AF: 0.00233 AC: 355AN: 152152Hom.: 2 Cov.: 32 AF XY: 0.00220 AC XY: 164AN XY: 74380
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
DSC3-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Aug 16, 2019 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Pathogenic
Dann
Benign
DEOGEN2
Uncertain
T;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D
M_CAP
Benign
D
MetaRNN
Benign
T;T
MetaSVM
Uncertain
T
MutationAssessor
Pathogenic
M;M
MutationTaster
Benign
D;D
PrimateAI
Benign
T
PROVEAN
Pathogenic
D;D
REVEL
Uncertain
Sift
Pathogenic
D;D
Sift4G
Pathogenic
D;D
Polyphen
D;D
Vest4
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at