chr6-31116117-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.

The NM_001264.5(CDSN):​c.1498C>T​(p.Arg500Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000807 in 1,610,904 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 31)
Exomes 𝑓: 0.0000075 ( 0 hom. )

Consequence

CDSN
NM_001264.5 missense

Scores

3
8
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.02
Variant links:
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 Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CDSNNM_001264.5 linkc.1498C>T p.Arg500Trp missense_variant 2/2 ENST00000376288.3 NP_001255.4 Q15517G8JLG2
PSORS1C1NM_014068.3 linkc.-229+1226G>A intron_variant ENST00000259881.10 NP_054787.2 Q9UIG5-1D2IYL0

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CDSNENST00000376288.3 linkc.1498C>T p.Arg500Trp missense_variant 2/21 NM_001264.5 ENSP00000365465.2 G8JLG2
PSORS1C1ENST00000259881.10 linkc.-229+1226G>A intron_variant 1 NM_014068.3 ENSP00000259881.9 Q9UIG5-1

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152138
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0000483
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000813
AC:
2
AN:
246076
Hom.:
0
AF XY:
0.00000746
AC XY:
1
AN XY:
133984
show subpopulations
Gnomad AFR exome
AF:
0.0000657
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000330
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000754
AC:
11
AN:
1458766
Hom.:
0
Cov.:
58
AF XY:
0.00000414
AC XY:
3
AN XY:
725334
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000720
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152138
Hom.:
0
Cov.:
31
AF XY:
0.0000135
AC XY:
1
AN XY:
74320
show subpopulations
Gnomad4 AFR
AF:
0.0000483
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000508
Hom.:
0
Bravo
AF:
0.00000378
ExAC
AF:
0.0000252
AC:
3

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpApr 15, 2024This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 500 of the CDSN protein (p.Arg500Trp). This variant is present in population databases (rs138408228, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with CDSN-related conditions. ClinVar contains an entry for this variant (Variation ID: 1978884). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on CDSN protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
-0.085
T
BayesDel_noAF
Benign
-0.18
CADD
Pathogenic
28
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.20
T
Eigen
Uncertain
0.30
Eigen_PC
Uncertain
0.25
FATHMM_MKL
Benign
0.75
D
LIST_S2
Uncertain
0.89
D
M_CAP
Uncertain
0.098
D
MetaRNN
Uncertain
0.74
D
MetaSVM
Benign
-1.1
T
PrimateAI
Uncertain
0.57
T
PROVEAN
Pathogenic
-7.4
D
REVEL
Uncertain
0.30
Sift
Pathogenic
0.0
D
Sift4G
Uncertain
0.0040
D
Vest4
0.71
MutPred
0.48
Loss of disorder (P = 0.0165);
MVP
0.39
MPC
1.0
ClinPred
0.99
D
GERP RS
3.1
gMVP
0.47

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: rs138408228; hg19: chr6-31083894; API