6-31116257-C-T
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_001264.5(CDSN):c.1358G>A(p.Ser453Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0125 in 1,614,052 control chromosomes in the GnomAD database, including 596 homozygotes. In-silico tool predicts a benign outcome for this variant. 10/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.0094 ( 37 hom., cov: 31)
Exomes 𝑓: 0.013 ( 559 hom. )
Consequence
CDSN
NM_001264.5 missense
NM_001264.5 missense
Scores
1
1
14
Clinical Significance
Conservation
PhyloP100: 0.0100
Genes affected
CDSN (HGNC:1802): (corneodesmosin) This gene encodes a protein found in corneodesmosomes, which localize to human epidermis and other cornified squamous epithelia. The encoded protein undergoes a series of cleavages during corneocyte maturation. This gene is highly polymorphic in human populations, and variation has been associated with skin diseases such as psoriasis, hypotrichosis and peeling skin syndrome. The gene is located in the major histocompatibility complex (MHC) class I region on chromosome 6. [provided by RefSeq, Dec 2014]
PSORS1C1 (HGNC:17202): (psoriasis susceptibility 1 candidate 1) This gene is one of several genes thought to confer susceptibility to psoriasis and systemic sclerosis, located on chromosome 6 near the major histocompatibility complex (MHC) class I region. [provided by RefSeq, Sep 2011]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.0015597343).
BP6
?
Variant 6-31116257-C-T is Benign according to our data. Variant chr6-31116257-C-T is described in ClinVar as [Benign]. Clinvar id is 802196.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
?
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0716 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CDSN | NM_001264.5 | c.1358G>A | p.Ser453Asn | missense_variant | 2/2 | ENST00000376288.3 | |
PSORS1C1 | NM_014068.3 | c.-229+1366C>T | intron_variant | ENST00000259881.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CDSN | ENST00000376288.3 | c.1358G>A | p.Ser453Asn | missense_variant | 2/2 | 1 | NM_001264.5 | P1 | |
PSORS1C1 | ENST00000259881.10 | c.-229+1366C>T | intron_variant | 1 | NM_014068.3 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.00935 AC: 1422AN: 152102Hom.: 37 Cov.: 31
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GnomAD3 exomes AF: 0.0177 AC: 4457AN: 251228Hom.: 122 AF XY: 0.0210 AC XY: 2854AN XY: 135798
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GnomAD4 exome AF: 0.0128 AC: 18719AN: 1461832Hom.: 559 Cov.: 58 AF XY: 0.0149 AC XY: 10869AN XY: 727212
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ClinVar
Significance: Benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 10, 2018 | This variant is associated with the following publications: (PMID: 25473393) - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
Peeling skin syndrome 1 Benign:1
Benign, criteria provided, single submitter | clinical testing | Mendelics | May 28, 2019 | - - |
CDSN-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Mar 08, 2019 | This variant is classified as 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
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationTaster
Benign
N;N
PrimateAI
Benign
T
PROVEAN
Benign
N
REVEL
Pathogenic
Sift
Benign
T
Sift4G
Benign
T
Vest4
MPC
ClinPred
T
GERP RS
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