18-31447808-C-T

Variant names:

• chr18-31447808-C-T
• rs8085532
• NM_001944.3:c.-70C>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.-70C>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 0.215 in 1,357,810 control chromosomes in the GnomAD database, including 35,187 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.27 (6677 hom., cov: 32)
  • Exomes 𝑓: 0.21 (28510 hom.)
• Consequence: DSG3 NM_001944.3 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.474
• Publications: 11 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=-0.8).
• BP6: Variant 18-31447808-C-T is Benign according to our data. Variant chr18-31447808-C-T is described in ClinVar as Benign. ClinVar VariationId is 1183480.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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DSG3	NM_001944.3	c.-70C>T		5_prime_UTR_variant	Exon 1 of 16	ENST00000257189.5	NP_001935.2
DSG3	XM_011525850.3	c.-70C>T		5_prime_UTR_variant	Exon 1 of 16		XP_011524152.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DSG3	ENST00000257189.5	c.-70C>T		5_prime_UTR_variant	Exon 1 of 16	1	NM_001944.3	ENSP00000257189.4

Frequencies

GnomAD3 genomes AF: 0.273 AC: 41498 AN: 151934 Hom.: 6654 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: 0.344

Gnomad FIN AF: 0.258

Gnomad MID AF: 0.143

Gnomad NFE AF: 0.195

Gnomad OTH AF: 0.238

GnomAD4 exome AF: 0.208 AC: 250838 AN: 1205756 Hom.: 28510 Cov.: 15 AF XY: 0.212 AC XY: 128345 AN XY: 606140

African (AFR) AF: 0.463 AC: 11644 AN: 25172

American (AMR) AF: 0.211 AC: 6081 AN: 28816

Ashkenazi Jewish (ASJ) AF: 0.204 AC: 4244 AN: 20812

East Asian (EAS) AF: 0.127 AC: 4369 AN: 34316

South Asian (SAS) AF: 0.346 AC: 23742 AN: 68642

European-Finnish (FIN) AF: 0.244 AC: 12478 AN: 51162

Middle Eastern (MID) AF: 0.198 AC: 991 AN: 5008

European-Non Finnish (NFE) AF: 0.191 AC: 176346 AN: 920908

Other (OTH) AF: 0.215 AC: 10943 AN: 50920

GnomAD4 genome AF: 0.273 AC: 41576 AN: 152054 Hom.: 6677 Cov.: 32 AF XY: 0.275 AC XY: 20400 AN XY: 74314

African (AFR) AF: 0.454 AC: 18836 AN: 41450

American (AMR) AF: 0.194 AC: 2957 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.205 AC: 713 AN: 3472

East Asian (EAS) AF: 0.144 AC: 747 AN: 5172

South Asian (SAS) AF: 0.345 AC: 1663 AN: 4826

European-Finnish (FIN) AF: 0.258 AC: 2726 AN: 10560

Middle Eastern (MID) AF: 0.144 AC: 42 AN: 292

European-Non Finnish (NFE) AF: 0.195 AC: 13272 AN: 67988

Other (OTH) AF: 0.237 AC: 501 AN: 2110

Alfa AF: 0.234 Hom.: 2317

Bravo AF: 0.274

Asia WGS AF: 0.227 AC: 793 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Nov 11, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	5.2
DANN	Benign	0.74
PhyloP100		-0.47
PromoterAI		0.0042	Neutral
Mutation Taster		=300/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs8085532; hg19: chr18-29027771; COSMIC: COSV105076668;