18-31456879-C-T

Variant names:

• chr18-31456879-C-T
• rs66889852
• NM_001944.3:c.85-114C>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.85-114C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000116 in 865,678 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 0.0000012 (0 hom.)
• Consequence: DSG3 NM_001944.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.765
• Publications: 0 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=-0.9).

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.85-114C>T		intron	N/A	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.85-114C>T		intron	N/A	ENSP00000257189.4	P32926
	DSG3	ENST00000851332.1		c.49-4348C>T		intron	N/A	ENSP00000521391.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000116 AC: 1 AN: 865678 Hom.: 0 AF XY: 0.00000228 AC XY: 1 AN XY: 438960

African (AFR) AF: 0.00 AC: 0 AN: 19762

American (AMR) AF: 0.00 AC: 0 AN: 23750

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16322

East Asian (EAS) AF: 0.00 AC: 0 AN: 34672

South Asian (SAS) AF: 0.0000209 AC: 1 AN: 47914

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46258

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2944

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 635040

Other (OTH) AF: 0.00 AC: 0 AN: 39016

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.65
DANN	Benign	0.41
PhyloP100		-0.77

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: rs66889852; hg19: chr18-29036842;