NM_001264.5:c.605T>C

Variant names:

• chr6-31117010-A-G
• rs707913
• NM_001264.5:c.605T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001264.5(CDSN):​c.605T>C​(p.Phe202Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.218 in 1,613,866 control chromosomes in the GnomAD database, including 41,221 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.27 (5986 hom., cov: 33)
  • Exomes 𝑓: 0.21 (35235 hom.)
• Consequence: CDSN NM_001264.5 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.71
• Publications: 30 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0037157536).
• BP6: Variant 6-31117010-A-G is Benign according to our data. Variant chr6-31117010-A-G is described in ClinVar as Benign. ClinVar VariationId is 1231588.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.374 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001264.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDSN	NM_001264.5	MANE Select	c.605T>C	p.Phe202Ser	missense	Exon 2 of 2	NP_001255.4
	PSORS1C1	NM_014068.3	MANE Select	c.-229+2119A>G		intron	N/A	NP_054787.2	Q9UIG5-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDSN	ENST00000376288.3	TSL:1 MANE Select	c.605T>C	p.Phe202Ser	missense	Exon 2 of 2	ENSP00000365465.2	Q15517
	PSORS1C1	ENST00000259881.10	TSL:1 MANE Select	c.-229+2119A>G		intron	N/A	ENSP00000259881.9	Q9UIG5-1
	PSORS1C1	ENST00000479581.5	TSL:1	n.61+2119A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.270 AC: 40984 AN: 151934 Hom.: 5979 Cov.: 33

Gnomad AFR AF: 0.380

Gnomad AMI AF: 0.105

Gnomad AMR AF: 0.316

Gnomad ASJ AF: 0.209

Gnomad EAS AF: 0.337

Gnomad SAS AF: 0.0872

Gnomad FIN AF: 0.202

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.216

Gnomad OTH AF: 0.265

GnomAD2 exomes AF: 0.233 AC: 58514 AN: 251430 AF XY: 0.218

Gnomad AFR exome AF: 0.380

Gnomad AMR exome AF: 0.325

Gnomad ASJ exome AF: 0.212

Gnomad EAS exome AF: 0.324

Gnomad FIN exome AF: 0.210

Gnomad NFE exome AF: 0.216

Gnomad OTH exome AF: 0.238

GnomAD4 exome AF: 0.212 AC: 310124 AN: 1461816 Hom.: 35235 Cov.: 75 AF XY: 0.207 AC XY: 150335 AN XY: 727216

African (AFR) AF: 0.380 AC: 12738 AN: 33478

American (AMR) AF: 0.322 AC: 14387 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.211 AC: 5520 AN: 26136

East Asian (EAS) AF: 0.321 AC: 12741 AN: 39700

South Asian (SAS) AF: 0.0778 AC: 6708 AN: 86258

European-Finnish (FIN) AF: 0.207 AC: 11056 AN: 53420

Middle Eastern (MID) AF: 0.167 AC: 963 AN: 5768

European-Non Finnish (NFE) AF: 0.210 AC: 233356 AN: 1111946

Other (OTH) AF: 0.210 AC: 12655 AN: 60392

GnomAD4 genome AF: 0.270 AC: 41023 AN: 152050 Hom.: 5986 Cov.: 33 AF XY: 0.266 AC XY: 19790 AN XY: 74328

African (AFR) AF: 0.379 AC: 15737 AN: 41480

American (AMR) AF: 0.316 AC: 4835 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.209 AC: 726 AN: 3472

East Asian (EAS) AF: 0.338 AC: 1739 AN: 5150

South Asian (SAS) AF: 0.0873 AC: 421 AN: 4822

European-Finnish (FIN) AF: 0.202 AC: 2143 AN: 10586

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.216 AC: 14708 AN: 67944

Other (OTH) AF: 0.267 AC: 563 AN: 2110

Alfa AF: 0.234 Hom.: 11201

Bravo AF: 0.287

TwinsUK AF: 0.226 AC: 838

ALSPAC AF: 0.217 AC: 838

ESP6500AA AF: 0.358 AC: 1578

ESP6500EA AF: 0.218 AC: 1876

ExAC AF: 0.231 AC: 28099

Asia WGS AF: 0.202 AC: 701 AN: 3478

EpiCase AF: 0.203

EpiControl AF: 0.208

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.050
BayesDel_addAF	Benign	-0.82	T
BayesDel_noAF	Benign	-0.81
CADD	Benign	13
DANN	Benign	0.44
DEOGEN2	Benign	0.0026	T
Eigen	Benign	-0.78
Eigen_PC	Benign	-0.92
FATHMM_MKL	Benign	0.00025	N
LIST_S2	Benign	0.22	T
MetaRNN	Benign	0.0037	T
MetaSVM	Benign	-0.91	T
PhyloP100		1.7
PrimateAI	Benign	0.38	T
PROVEAN	Benign	3.0	N
REVEL	Benign	0.044
Sift	Benign	0.55	T
Sift4G	Benign	1.0	T
Vest4		0.020
MPC		0.56
ClinPred		0.00088	T
GERP RS		1.4
gMVP		0.064
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs707913; hg19: chr6-31084787; COSMIC: COSV52538230; COSMIC: COSV52538230;