18-31453763-T-C

Position:

• chr18-31453763-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001944.3(DSG3):​c.49-2677T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.27 in 151,904 control chromosomes in the GnomAD database, including 6,186 homozygotes. 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: 𝑓 0.27 (6186 hom., cov: 32)
• Consequence: DSG3 NM_001944.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.85

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.41 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DSG3	NM_001944.3	c.49-2677T>C		intron_variant		ENST00000257189.5	NP_001935.2
DSG3	XM_011525850.3	c.49-2677T>C		intron_variant			XP_011524152.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DSG3	ENST00000257189.5	c.49-2677T>C		intron_variant		1	NM_001944.3	ENSP00000257189.4

Frequencies

GnomAD3 genomes AF: 0.270 AC: 40974 AN: 151786 Hom.: 6167 Cov.: 32

Gnomad AFR AF: 0.415

Gnomad AMI AF: 0.134

Gnomad AMR AF: 0.197

Gnomad ASJ AF: 0.210

Gnomad EAS AF: 0.156

Gnomad SAS AF: 0.356

Gnomad FIN AF: 0.275

Gnomad MID AF: 0.156

Gnomad NFE AF: 0.207

Gnomad OTH AF: 0.239

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.270 AC: 41044 AN: 151904 Hom.: 6186 Cov.: 32 AF XY: 0.272 AC XY: 20235 AN XY: 74260

Gnomad4 AFR AF: 0.415

Gnomad4 AMR AF: 0.197

Gnomad4 ASJ AF: 0.210

Gnomad4 EAS AF: 0.156

Gnomad4 SAS AF: 0.356

Gnomad4 FIN AF: 0.275

Gnomad4 NFE AF: 0.207

Gnomad4 OTH AF: 0.237

Alfa AF: 0.210 Hom.: 3073

Bravo AF: 0.268

Asia WGS AF: 0.236 AC: 821 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.49
DANN	Benign	0.37

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

Publications

LitVar

Other links and lift over

dbSNP: rs3911655; hg19: chr18-29033726;