rs1466379

Positions:

• chr18-31476502-A-G
• chr18-31476502-A-T

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.*242A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.185 in 395,736 control chromosomes in the GnomAD database, including 8,745 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.22 (5048 hom., cov: 32)
  • Exomes 𝑓: 0.16 (3697 hom.)
• Consequence: DSG3 NM_001944.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0720

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=-0.91).
• BP6: Variant 18-31476502-A-G is Benign according to our data. Variant chr18-31476502-A-G is described in ClinVar as [Benign]. Clinvar id is 1180073.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.421 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DSG3	NM_001944.3	c.*242A>G		3_prime_UTR_variant	16/16	ENST00000257189.5	NP_001935.2
DSG3	XM_011525850.3	c.*242A>G		3_prime_UTR_variant	16/16		XP_011524152.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DSG3	ENST00000257189.5	c.*242A>G		3_prime_UTR_variant	16/16	1	NM_001944.3	ENSP00000257189.4

Frequencies

GnomAD3 genomes AF: 0.223 AC: 33827 AN: 152008 Hom.: 5021 Cov.: 32

Gnomad AFR AF: 0.426

Gnomad AMI AF: 0.0910

Gnomad AMR AF: 0.146

Gnomad ASJ AF: 0.114

Gnomad EAS AF: 0.132

Gnomad SAS AF: 0.219

Gnomad FIN AF: 0.156

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.143

Gnomad OTH AF: 0.193

GnomAD4 exome AF: 0.162 AC: 39445 AN: 243610 Hom.: 3697 Cov.: 4 AF XY: 0.160 AC XY: 19818 AN XY: 123704

Gnomad4 AFR exome AF: 0.436

Gnomad4 AMR exome AF: 0.125

Gnomad4 ASJ exome AF: 0.126

Gnomad4 EAS exome AF: 0.174

Gnomad4 SAS exome AF: 0.236

Gnomad4 FIN exome AF: 0.172

Gnomad4 NFE exome AF: 0.147

Gnomad4 OTH exome AF: 0.174

GnomAD4 genome AF: 0.223 AC: 33907 AN: 152126 Hom.: 5048 Cov.: 32 AF XY: 0.220 AC XY: 16368 AN XY: 74348

Gnomad4 AFR AF: 0.426

Gnomad4 AMR AF: 0.146

Gnomad4 ASJ AF: 0.114

Gnomad4 EAS AF: 0.132

Gnomad4 SAS AF: 0.219

Gnomad4 FIN AF: 0.156

Gnomad4 NFE AF: 0.143

Gnomad4 OTH AF: 0.193

Alfa AF: 0.159 Hom.: 3090

Bravo AF: 0.228

Asia WGS AF: 0.210 AC: 733 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	-0.91
CADD	Benign	1.8
DANN	Benign	0.64

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: rs1466379; hg19: chr18-29056465;