18-30993914-T-TAA

Position:

• chr18-30993914-T-TAA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001941.5(DSC3):​c.*259_*260dupTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0226 in 300,022 control chromosomes in the GnomAD database, including 312 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.035 (312 hom., cov: 31)
  • Exomes 𝑓: 0.011 (0 hom.)
• Consequence: DSC3 NM_001941.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.391

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 -10 ACMG points.

• BP6: Variant 18-30993914-T-TAA is Benign according to our data. Variant chr18-30993914-T-TAA is described in ClinVar as [Benign]. Clinvar id is 1253461.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.117 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DSC3	NM_001941.5	c.*259_*260dupTT		3_prime_UTR_variant	16/16	ENST00000360428.9	NP_001932.2
DSC3	NM_024423.4	c.*473_*474dupTT		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.*259_*260dupTT		3_prime_UTR_variant	16/16	1	NM_001941.5	ENSP00000353608.4
DSC3	ENST00000434452	c.*473_*474dupTT		3_prime_UTR_variant	17/17	5		ENSP00000392068.1

Frequencies

GnomAD3 genomes AF: 0.0345 AC: 4976 AN: 144098 Hom.: 311 Cov.: 31

Gnomad AFR AF: 0.119

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0101

Gnomad ASJ AF: 0.000592

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000656

Gnomad FIN AF: 0.000117

Gnomad MID AF: 0.00331

Gnomad NFE AF: 0.000337

Gnomad OTH AF: 0.0244

GnomAD4 exome AF: 0.0114 AC: 1783 AN: 155874 Hom.: 0 Cov.: 0 AF XY: 0.0113 AC XY: 935 AN XY: 82810

Gnomad4 AFR exome AF: 0.0881

Gnomad4 AMR exome AF: 0.0108

Gnomad4 ASJ exome AF: 0.00768

Gnomad4 EAS exome AF: 0.0100

Gnomad4 SAS exome AF: 0.00982

Gnomad4 FIN exome AF: 0.00695

Gnomad4 NFE exome AF: 0.00875

Gnomad4 OTH exome AF: 0.0114

GnomAD4 genome AF: 0.0346 AC: 4984 AN: 144148 Hom.: 312 Cov.: 31 AF XY: 0.0332 AC XY: 2321 AN XY: 69880

Gnomad4 AFR AF: 0.119

Gnomad4 AMR AF: 0.0101

Gnomad4 ASJ AF: 0.000592

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000438

Gnomad4 FIN AF: 0.000117

Gnomad4 NFE AF: 0.000337

Gnomad4 OTH AF: 0.0242

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2021

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Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1222542700; hg19: chr18-28573880;