18-30997313-C-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001941.5(DSC3):c.2236-265G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.259 in 151,952 control chromosomes in the GnomAD database, including 5,743 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.26 (5743 hom., cov: 32)
• Consequence: DSC3 NM_001941.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.302

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BP6: Variant 18-30997313-C-G is Benign according to our data. Variant chr18-30997313-C-G is described in ClinVar as [Benign]. Clinvar id is 1240769.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.589 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DSC3	NM_001941.5	c.2236-265G>C		intron_variant		ENST00000360428.9
DSC3	NM_024423.4	c.2236-265G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DSC3	ENST00000360428.9	c.2236-265G>C		intron_variant		1	NM_001941.5	P1
DSC3	ENST00000434452.5	c.2236-265G>C		intron_variant		5
DSC3	ENST00000584980.1	c.360-265G>C		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.260 AC: 39419 AN: 151832 Hom.: 5744 Cov.: 32

Gnomad AFR AF: 0.158

Gnomad AMI AF: 0.343

Gnomad AMR AF: 0.206

Gnomad ASJ AF: 0.211

Gnomad EAS AF: 0.607

Gnomad SAS AF: 0.395

Gnomad FIN AF: 0.345

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.286

Gnomad OTH AF: 0.259

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.259 AC: 39426 AN: 151952 Hom.: 5743 Cov.: 32 AF XY: 0.265 AC XY: 19670 AN XY: 74248

Gnomad4 AFR AF: 0.158

Gnomad4 AMR AF: 0.206

Gnomad4 ASJ AF: 0.211

Gnomad4 EAS AF: 0.606

Gnomad4 SAS AF: 0.394

Gnomad4 FIN AF: 0.345

Gnomad4 NFE AF: 0.286

Gnomad4 OTH AF: 0.258

Alfa AF: 0.264 Hom.: 691

Bravo AF: 0.241

Asia WGS AF: 0.438 AC: 1522 AN: 3478

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

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
Cadd	Benign	0.58
Dann	Benign	0.40

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: rs1313577; hg19: chr18-28577279;