chr18-31447794-C-T

Variant names:

• chr18-31447794-C-T
• rs8085523
• NM_001944.3:c.-84C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.133
• Publications: 9 publications found

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]

DSG3 Gene-Disease associations (from GenCC):

• blistering, acantholytic, of oral and laryngeal mucosa

  Inheritance: Unknown, AR Classification: MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Benign. The variant received -20 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 VariationId is 1267671.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.449 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001944.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DSG3	NM_001944.3	MANE Select	c.-84C>T		5_prime_UTR	Exon 1 of 16	NP_001935.2	P32926

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DSG3	ENST00000257189.5	TSL:1 MANE Select	c.-84C>T		5_prime_UTR	Exon 1 of 16	ENSP00000257189.4	P32926
	DSG3	ENST00000851332.1		c.-84C>T		upstream_gene	N/A	ENSP00000521391.1

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

African (AFR) AF: 0.465 AC: 10329 AN: 22200

American (AMR) AF: 0.210 AC: 5624 AN: 26816

Ashkenazi Jewish (ASJ) AF: 0.201 AC: 3809 AN: 18940

East Asian (EAS) AF: 0.127 AC: 4191 AN: 33102

South Asian (SAS) AF: 0.344 AC: 21553 AN: 62692

European-Finnish (FIN) AF: 0.244 AC: 12265 AN: 50308

Middle Eastern (MID) AF: 0.198 AC: 926 AN: 4670

European-Non Finnish (NFE) AF: 0.193 AC: 152334 AN: 790154

Other (OTH) AF: 0.216 AC: 9875 AN: 45734

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

African (AFR) AF: 0.454 AC: 18816 AN: 41442

American (AMR) AF: 0.194 AC: 2958 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.205 AC: 712 AN: 3466

East Asian (EAS) AF: 0.144 AC: 746 AN: 5176

South Asian (SAS) AF: 0.345 AC: 1662 AN: 4820

European-Finnish (FIN) AF: 0.258 AC: 2723 AN: 10552

Middle Eastern (MID) AF: 0.143 AC: 42 AN: 294

European-Non Finnish (NFE) AF: 0.195 AC: 13272 AN: 67980

Other (OTH) AF: 0.237 AC: 501 AN: 2114

Alfa AF: 0.222 Hom.: 11408

Bravo AF: 0.274

Asia WGS AF: 0.227 AC: 793 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.9
DANN	Benign	0.78
PhyloP100		0.13
PromoterAI		-0.014	Neutral
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

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