18-30993914-T-TA

Position:

• chr18-30993914-T-TA

Variant summary

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

The NM_001941.5(DSC3):​c.*260_*261insT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.163 in 294,890 control chromosomes in the GnomAD database, including 300 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.040 (295 hom., cov: 31)
  • Exomes 𝑓: 0.28 (5 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-TA is Benign according to our data. Variant chr18-30993914-T-TA is described in ClinVar as [Benign]. Clinvar id is 1242844.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.121 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DSC3	NM_001941.5	c.*260_*261insT		3_prime_UTR_variant	16/16	ENST00000360428.9
DSC3	NM_024423.4	c.*474_*475insT		3_prime_UTR_variant	17/17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DSC3	ENST00000360428.9	c.*260_*261insT		3_prime_UTR_variant	16/16	1	NM_001941.5	P1
DSC3	ENST00000434452.5	c.*474_*475insT		3_prime_UTR_variant	17/17	5

Frequencies

GnomAD3 genomes AF: 0.0399 AC: 5726 AN: 143568 Hom.: 295 Cov.: 31

Gnomad AFR AF: 0.124

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0165

Gnomad ASJ AF: 0.00297

Gnomad EAS AF: 0.00338

Gnomad SAS AF: 0.00350

Gnomad FIN AF: 0.0208

Gnomad MID AF: 0.00667

Gnomad NFE AF: 0.00422

Gnomad OTH AF: 0.0342

GnomAD4 exome AF: 0.280 AC: 42299 AN: 151274 Hom.: 5 Cov.: 0 AF XY: 0.278 AC XY: 22392 AN XY: 80468

Gnomad4 AFR exome AF: 0.264

Gnomad4 AMR exome AF: 0.323

Gnomad4 ASJ exome AF: 0.269

Gnomad4 EAS exome AF: 0.279

Gnomad4 SAS exome AF: 0.284

Gnomad4 FIN exome AF: 0.265

Gnomad4 NFE exome AF: 0.279

Gnomad4 OTH exome AF: 0.275

GnomAD4 genome AF: 0.0399 AC: 5734 AN: 143616 Hom.: 295 Cov.: 31 AF XY: 0.0394 AC XY: 2739 AN XY: 69552

Gnomad4 AFR AF: 0.124

Gnomad4 AMR AF: 0.0165

Gnomad4 ASJ AF: 0.00297

Gnomad4 EAS AF: 0.00339

Gnomad4 SAS AF: 0.00416

Gnomad4 FIN AF: 0.0208

Gnomad4 NFE AF: 0.00422

Gnomad4 OTH AF: 0.0340

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 20, 2021

- -

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs1222542700; hg19: chr18-28573880;