18-31459798-T-C

Position:

• chr18-31459798-T-C

Variant summary

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

The NM_001944.3(DSG3):​c.518-47T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.103 in 1,501,888 control chromosomes in the GnomAD database, including 8,360 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.11 (970 hom., cov: 32)
  • Exomes 𝑓: 0.10 (7390 hom.)
• Consequence: DSG3 NM_001944.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.968

Genes affected

DSG3 (HGNC:3050): (desmoglein 3) This gene encodes a member of the desmoglein family and cadherin cell adhesion molecule superfamily of proteins. Desmogleins are calcium-binding transmembrane glycoprotein components of desmosomes, cell-cell junctions between epithelial, myocardial, and other cell types. The encoded preproprotein is proteolytically processed to generate the mature glycoprotein. This gene is present in a gene cluster with other desmoglein gene family members on chromosome 18. The encoded protein has been identified as the autoantigen of the autoimmune blistering disease pemphigus vulgaris. [provided by RefSeq, Jan 2016]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 18-31459798-T-C is Benign according to our data. Variant chr18-31459798-T-C is described in ClinVar as [Benign]. Clinvar id is 1290293.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.121 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DSG3	NM_001944.3	c.518-47T>C		intron_variant		ENST00000257189.5
DSG3	XM_011525850.3	c.518-47T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DSG3	ENST00000257189.5	c.518-47T>C		intron_variant		1	NM_001944.3	P1

Frequencies

GnomAD3 genomes AF: 0.106 AC: 16200 AN: 152124 Hom.: 969 Cov.: 32

Gnomad AFR AF: 0.124

Gnomad AMI AF: 0.0713

Gnomad AMR AF: 0.0854

Gnomad ASJ AF: 0.0936

Gnomad EAS AF: 0.0908

Gnomad SAS AF: 0.112

Gnomad FIN AF: 0.103

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.103

Gnomad OTH AF: 0.0984

GnomAD3 exomes AF: 0.105 AC: 22178 AN: 211170 Hom.: 1225 AF XY: 0.106 AC XY: 12075 AN XY: 113888

Gnomad AFR exome AF: 0.131

Gnomad AMR exome AF: 0.0614

Gnomad ASJ exome AF: 0.112

Gnomad EAS exome AF: 0.0952

Gnomad SAS exome AF: 0.117

Gnomad FIN exome AF: 0.111

Gnomad NFE exome AF: 0.110

Gnomad OTH exome AF: 0.108

GnomAD4 exome AF: 0.103 AC: 138761 AN: 1349646 Hom.: 7390 Cov.: 19 AF XY: 0.103 AC XY: 68978 AN XY: 668702

Gnomad4 AFR exome AF: 0.129

Gnomad4 AMR exome AF: 0.0651

Gnomad4 ASJ exome AF: 0.103

Gnomad4 EAS exome AF: 0.107

Gnomad4 SAS exome AF: 0.115

Gnomad4 FIN exome AF: 0.113

Gnomad4 NFE exome AF: 0.102

Gnomad4 OTH exome AF: 0.101

GnomAD4 genome AF: 0.106 AC: 16212 AN: 152242 Hom.: 970 Cov.: 32 AF XY: 0.105 AC XY: 7841 AN XY: 74434

Gnomad4 AFR AF: 0.124

Gnomad4 AMR AF: 0.0853

Gnomad4 ASJ AF: 0.0936

Gnomad4 EAS AF: 0.0910

Gnomad4 SAS AF: 0.112

Gnomad4 FIN AF: 0.103

Gnomad4 NFE AF: 0.103

Gnomad4 OTH AF: 0.0997

Alfa AF: 0.104 Hom.: 207

Bravo AF: 0.105

Asia WGS AF: 0.131 AC: 453 AN: 3478

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	Nov 11, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.0
DANN	Benign	0.63

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: rs3737365; hg19: chr18-29039761;