18-30996567-A-C

Position:

• chr18-30996567-A-C

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.2493+224T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.158 in 152,086 control chromosomes in the GnomAD database, including 3,033 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.16 (3033 hom., cov: 32)
• Consequence: DSC3 NM_001941.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.731

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 18-30996567-A-C is Benign according to our data. Variant chr18-30996567-A-C is described in ClinVar as [Benign]. Clinvar id is 1233670.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.339 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DSC3	NM_001941.5	c.2493+224T>G		intron_variant		ENST00000360428.9	NP_001932.2
DSC3	NM_024423.4	c.2493+224T>G		intron_variant			NP_077741.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DSC3	ENST00000360428.9	c.2493+224T>G		intron_variant		1	NM_001941.5	ENSP00000353608.4
DSC3	ENST00000434452.5	c.2493+224T>G		intron_variant		5		ENSP00000392068.1
DSC3	ENST00000584980.1	c.615+224T>G		intron_variant		5		ENSP00000464283.1

Frequencies

GnomAD3 genomes AF: 0.158 AC: 23941 AN: 151968 Hom.: 3022 Cov.: 32

Gnomad AFR AF: 0.343

Gnomad AMI AF: 0.116

Gnomad AMR AF: 0.174

Gnomad ASJ AF: 0.117

Gnomad EAS AF: 0.140

Gnomad SAS AF: 0.141

Gnomad FIN AF: 0.0214

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.0676

Gnomad OTH AF: 0.149

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

GnomAD4 genome AF: 0.158 AC: 23994 AN: 152086 Hom.: 3033 Cov.: 32 AF XY: 0.153 AC XY: 11397 AN XY: 74382

Gnomad4 AFR AF: 0.344

Gnomad4 AMR AF: 0.174

Gnomad4 ASJ AF: 0.117

Gnomad4 EAS AF: 0.141

Gnomad4 SAS AF: 0.142

Gnomad4 FIN AF: 0.0214

Gnomad4 NFE AF: 0.0676

Gnomad4 OTH AF: 0.150

Alfa AF: 0.0908 Hom.: 649

Bravo AF: 0.179

Asia WGS AF: 0.153 AC: 531 AN: 3468

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 11, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.40
DANN	Benign	0.73

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: rs1789051; hg19: chr18-28576533;