18-31447794-C-T

Position:

• chr18-31447794-C-T

Variant summary

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

The NM_001944.3(DSG3):​c.-84C>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 0.218 in 1,206,648 control chromosomes in the GnomAD database, including 31,862 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.27 (6663 hom., cov: 32)
  • Exomes 𝑓: 0.21 (25199 hom.)
• Consequence: DSG3 NM_001944.3 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.133

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 18-31447794-C-T is Benign according to our data. Variant chr18-31447794-C-T is described in ClinVar as [Benign]. Clinvar id is 1267671.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.449 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DSG3	NM_001944.3	c.-84C>T		5_prime_UTR_variant	1/16	ENST00000257189.5
DSG3	XM_011525850.3	c.-84C>T		5_prime_UTR_variant	1/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DSG3	ENST00000257189.5	c.-84C>T		5_prime_UTR_variant	1/16	1	NM_001944.3	P1

Frequencies

GnomAD3 genomes AF: 0.273 AC: 41475 AN: 151914 Hom.: 6641 Cov.: 32

Gnomad AFR AF: 0.454

Gnomad AMI AF: 0.130

Gnomad AMR AF: 0.193

Gnomad ASJ AF: 0.205

Gnomad EAS AF: 0.145

Gnomad SAS AF: 0.345

Gnomad FIN AF: 0.258

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.195

Gnomad OTH AF: 0.238

GnomAD4 exome AF: 0.209 AC: 220906 AN: 1054616 Hom.: 25199 Cov.: 13 AF XY: 0.213 AC XY: 113856 AN XY: 533858

Gnomad4 AFR exome AF: 0.465

Gnomad4 AMR exome AF: 0.210

Gnomad4 ASJ exome AF: 0.201

Gnomad4 EAS exome AF: 0.127

Gnomad4 SAS exome AF: 0.344

Gnomad4 FIN exome AF: 0.244

Gnomad4 NFE exome AF: 0.193

Gnomad4 OTH exome AF: 0.216

GnomAD4 genome AF: 0.273 AC: 41551 AN: 152032 Hom.: 6663 Cov.: 32 AF XY: 0.274 AC XY: 20393 AN XY: 74304

Gnomad4 AFR AF: 0.454

Gnomad4 AMR AF: 0.194

Gnomad4 ASJ AF: 0.205

Gnomad4 EAS AF: 0.144

Gnomad4 SAS AF: 0.345

Gnomad4 FIN AF: 0.258

Gnomad4 NFE AF: 0.195

Gnomad4 OTH AF: 0.237

Alfa AF: 0.201 Hom.: 5444

Bravo AF: 0.274

Asia WGS AF: 0.227 AC: 793 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

Jun 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.9
DANN	Benign	0.78

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs8085523; hg19: chr18-29027757; COSMIC: COSV57127521;