18-30994031-T-C

Position:

• chr18-30994031-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001941.5(DSC3):​c.*144A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00857 in 827,808 control chromosomes in the GnomAD database, including 345 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.031 (236 hom., cov: 32)
  • Exomes 𝑓: 0.0034 (109 hom.)
• Consequence: DSC3 NM_001941.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.164

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 18-30994031-T-C is Benign according to our data. Variant chr18-30994031-T-C is described in ClinVar as [Benign]. Clinvar id is 1221013.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.106 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DSC3	NM_001941.5	c.*144A>G		3_prime_UTR_variant	16/16	ENST00000360428.9	NP_001932.2
DSC3	NM_024423.4	c.*358A>G		3_prime_UTR_variant	17/17		NP_077741.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DSC3	ENST00000360428	c.*144A>G		3_prime_UTR_variant	16/16	1	NM_001941.5	ENSP00000353608.4
DSC3	ENST00000434452	c.*358A>G		3_prime_UTR_variant	17/17	5		ENSP00000392068.1

Frequencies

GnomAD3 genomes AF: 0.0313 AC: 4771 AN: 152186 Hom.: 236 Cov.: 32

Gnomad AFR AF: 0.109

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0111

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000470

Gnomad OTH AF: 0.0273

GnomAD4 exome AF: 0.00343 AC: 2319 AN: 675504 Hom.: 109 Cov.: 9 AF XY: 0.00290 AC XY: 1013 AN XY: 349032

Gnomad4 AFR exome AF: 0.107

Gnomad4 AMR exome AF: 0.00714

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000279

Gnomad4 FIN exome AF: 0.000297

Gnomad4 NFE exome AF: 0.000277

Gnomad4 OTH exome AF: 0.00731

GnomAD4 genome AF: 0.0314 AC: 4778 AN: 152304 Hom.: 236 Cov.: 32 AF XY: 0.0307 AC XY: 2288 AN XY: 74488

Gnomad4 AFR AF: 0.109

Gnomad4 AMR AF: 0.0110

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.000188

Gnomad4 NFE AF: 0.000470

Gnomad4 OTH AF: 0.0270

Alfa AF: 0.0352 Hom.: 15

Bravo AF: 0.0367

Asia WGS AF: 0.00491 AC: 17 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 19, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.5
DANN	Benign	0.73

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs9949290; hg19: chr18-28573997;