18-31476502-A-T

Variant names:

• chr18-31476502-A-T
• rs1466379
• NM_001944.3:c.*242A>T

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.*242A>T variant causes a 3 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 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0720
• Publications: 7 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=-0.82).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DSG3	NM_001944.3	c.*242A>T		3_prime_UTR_variant	Exon 16 of 16	ENST00000257189.5	NP_001935.2
DSG3	XM_011525850.3	c.*242A>T		3_prime_UTR_variant	Exon 16 of 16		XP_011524152.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DSG3	ENST00000257189.5	c.*242A>T		3_prime_UTR_variant	Exon 16 of 16	1	NM_001944.3	ENSP00000257189.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 244034 Hom.: 0 Cov.: 4 AF XY: 0.00 AC XY: 0 AN XY: 123906

African (AFR) AF: 0.00 AC: 0 AN: 7128

American (AMR) AF: 0.00 AC: 0 AN: 8918

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 8476

East Asian (EAS) AF: 0.00 AC: 0 AN: 20098

South Asian (SAS) AF: 0.00 AC: 0 AN: 6458

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 16382

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1192

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 159824

Other (OTH) AF: 0.00 AC: 0 AN: 15558

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.6
DANN	Benign	0.68
PhyloP100		-0.072

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: rs1466379; hg19: chr18-29056465;