18-31447794-C-A

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001944.3(DSG3):​c.-84C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: DSG3 NM_001944.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).

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>A		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>A		5_prime_UTR	Exon 1 of 16	ENSP00000257189.4	P32926
	DSG3	ENST00000851332.1		c.-84C>A		upstream_gene	N/A	ENSP00000521391.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1057180 Hom.: 0 Cov.: 13 AF XY: 0.00 AC XY: 0 AN XY: 535170

African (AFR) AF: 0.00 AC: 0 AN: 22274

American (AMR) AF: 0.00 AC: 0 AN: 26870

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18980

East Asian (EAS) AF: 0.00 AC: 0 AN: 33140

South Asian (SAS) AF: 0.00 AC: 0 AN: 62948

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50374

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4680

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 792082

Other (OTH) AF: 0.00 AC: 0 AN: 45832

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 11408

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	4.9
DANN	Benign	0.70
PhyloP100		0.13
PromoterAI		0.013	Neutral

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;