rs3848485

chr18-31456353-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001944.3(DSG3):c.49-87A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.227 in 864,172 control chromosomes in the GnomAD database, including 24,584 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.28 (6693 hom., cov: 32)
  • Exomes 𝑓: 0.22 (17891 hom.)
• Consequence: DSG3 NM_001944.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0100

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 18-31456353-A-G is Benign according to our data. Variant chr18-31456353-A-G is described in ClinVar as [Benign]. Clinvar id is 1182152.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.439 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DSG3	NM_001944.3	c.49-87A>G		intron_variant		ENST00000257189.5
DSG3	XM_011525850.3	c.49-87A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DSG3	ENST00000257189.5	c.49-87A>G		intron_variant		1	NM_001944.3	P1

Frequencies

GnomAD3 genomes AF: 0.278 AC: 42267 AN: 151964 Hom.: 6663 Cov.: 32

Gnomad AFR AF: 0.443

Gnomad AMI AF: 0.134

Gnomad AMR AF: 0.200

Gnomad ASJ AF: 0.209

Gnomad EAS AF: 0.154

Gnomad SAS AF: 0.361

Gnomad FIN AF: 0.275

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.206

Gnomad OTH AF: 0.243

GnomAD4 exome AF: 0.216 AC: 153705 AN: 712090 Hom.: 17891 AF XY: 0.216 AC XY: 76399 AN XY: 353706

Gnomad4 AFR exome AF: 0.462

Gnomad4 AMR exome AF: 0.226

Gnomad4 ASJ exome AF: 0.197

Gnomad4 EAS exome AF: 0.154

Gnomad4 SAS exome AF: 0.370

Gnomad4 FIN exome AF: 0.266

Gnomad4 NFE exome AF: 0.202

Gnomad4 OTH exome AF: 0.229

GnomAD4 genome AF: 0.278 AC: 42354 AN: 152082 Hom.: 6693 Cov.: 32 AF XY: 0.281 AC XY: 20872 AN XY: 74358

Gnomad4 AFR AF: 0.444

Gnomad4 AMR AF: 0.201

Gnomad4 ASJ AF: 0.209

Gnomad4 EAS AF: 0.154

Gnomad4 SAS AF: 0.361

Gnomad4 FIN AF: 0.275

Gnomad4 NFE AF: 0.207

Gnomad4 OTH AF: 0.242

Alfa AF: 0.254 Hom.: 880

Bravo AF: 0.277

Asia WGS AF: 0.243 AC: 846 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	3.4
Dann	Benign	0.70

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: rs3848485; hg19: chr18-29036316; COSMIC: COSV57129712;