18-31456879-C-G

Position:

• chr18-31456879-C-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001944.3(DSG3):​c.85-114C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0259 in 1,017,686 control chromosomes in the GnomAD database, including 936 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.056 (491 hom., cov: 32)
  • Exomes 𝑓: 0.021 (445 hom.)
• Consequence: DSG3 NM_001944.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.765

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 18-31456879-C-G is Benign according to our data. Variant chr18-31456879-C-G is described in ClinVar as [Benign]. Clinvar id is 1284172.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.151 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DSG3	NM_001944.3	c.85-114C>G		intron_variant		ENST00000257189.5	NP_001935.2
DSG3	XM_011525850.3	c.85-114C>G		intron_variant			XP_011524152.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DSG3	ENST00000257189.5	c.85-114C>G		intron_variant		1	NM_001944.3	ENSP00000257189	P1

Frequencies

GnomAD3 genomes AF: 0.0559 AC: 8503 AN: 152100 Hom.: 490 Cov.: 32

Gnomad AFR AF: 0.154

Gnomad AMI AF: 0.0197

Gnomad AMR AF: 0.0226

Gnomad ASJ AF: 0.00346

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00518

Gnomad FIN AF: 0.0433

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0174

Gnomad OTH AF: 0.0430

GnomAD4 exome AF: 0.0206 AC: 17802 AN: 865468 Hom.: 445 AF XY: 0.0197 AC XY: 8646 AN XY: 438862

Gnomad4 AFR exome AF: 0.159

Gnomad4 AMR exome AF: 0.0173

Gnomad4 ASJ exome AF: 0.00392

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00511

Gnomad4 FIN exome AF: 0.0426

Gnomad4 NFE exome AF: 0.0171

Gnomad4 OTH exome AF: 0.0246

GnomAD4 genome AF: 0.0560 AC: 8521 AN: 152218 Hom.: 491 Cov.: 32 AF XY: 0.0547 AC XY: 4069 AN XY: 74444

Gnomad4 AFR AF: 0.154

Gnomad4 AMR AF: 0.0226

Gnomad4 ASJ AF: 0.00346

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00498

Gnomad4 FIN AF: 0.0433

Gnomad4 NFE AF: 0.0174

Gnomad4 OTH AF: 0.0426

Alfa AF: 0.0400 Hom.: 33

Bravo AF: 0.0582

Asia WGS AF: 0.00982 AC: 36 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 19, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.52
DANN	Benign	0.50

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: rs66889852; hg19: chr18-29036842;