18-31447782-C-T

Position:

• chr18-31447782-C-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.-96C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.185 in 992,842 control chromosomes in the GnomAD database, including 18,144 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.18 (2418 hom., cov: 33)
  • Exomes 𝑓: 0.19 (15726 hom.)
• Consequence: DSG3 NM_001944.3 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.366

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=-0.75).
• BP6: Variant 18-31447782-C-T is Benign according to our data. Variant chr18-31447782-C-T is described in ClinVar as [Benign]. Clinvar id is 1225011.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.319 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DSG3	NM_001944.3	c.-96C>T		5_prime_UTR_variant	1/16	ENST00000257189.5	NP_001935.2
DSG3	XM_011525850.3	c.-96C>T		5_prime_UTR_variant	1/16		XP_011524152.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DSG3	ENST00000257189.5	c.-96C>T		5_prime_UTR_variant	1/16	1	NM_001944.3	ENSP00000257189	P1

Frequencies

GnomAD3 genomes AF: 0.176 AC: 26734 AN: 152002 Hom.: 2413 Cov.: 33

Gnomad AFR AF: 0.158

Gnomad AMI AF: 0.111

Gnomad AMR AF: 0.151

Gnomad ASJ AF: 0.202

Gnomad EAS AF: 0.145

Gnomad SAS AF: 0.332

Gnomad FIN AF: 0.215

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.177

Gnomad OTH AF: 0.163

GnomAD4 exome AF: 0.187 AC: 157204 AN: 840720 Hom.: 15726 Cov.: 11 AF XY: 0.193 AC XY: 82893 AN XY: 430372

Gnomad4 AFR exome AF: 0.156

Gnomad4 AMR exome AF: 0.192

Gnomad4 ASJ exome AF: 0.200

Gnomad4 EAS exome AF: 0.126

Gnomad4 SAS exome AF: 0.336

Gnomad4 FIN exome AF: 0.200

Gnomad4 NFE exome AF: 0.177

Gnomad4 OTH exome AF: 0.181

GnomAD4 genome AF: 0.176 AC: 26772 AN: 152122 Hom.: 2418 Cov.: 33 AF XY: 0.180 AC XY: 13349 AN XY: 74352

Gnomad4 AFR AF: 0.159

Gnomad4 AMR AF: 0.152

Gnomad4 ASJ AF: 0.202

Gnomad4 EAS AF: 0.145

Gnomad4 SAS AF: 0.332

Gnomad4 FIN AF: 0.215

Gnomad4 NFE AF: 0.177

Gnomad4 OTH AF: 0.163

Alfa AF: 0.177 Hom.: 450

Bravo AF: 0.166

Asia WGS AF: 0.199 AC: 692 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	Jun 19, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	9.7
DANN	Benign	0.71

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs10084010; hg19: chr18-29027745;