18-31457168-T-C

Position:

• chr18-31457168-T-C

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.216+44T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.103 in 1,569,704 control chromosomes in the GnomAD database, including 8,574 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.10 (910 hom., cov: 32)
  • Exomes 𝑓: 0.10 (7664 hom.)
• Consequence: DSG3 NM_001944.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.273

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=-0.78).
• BP6: Variant 18-31457168-T-C is Benign according to our data. Variant chr18-31457168-T-C is described in ClinVar as [Benign]. Clinvar id is 1228227.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.112 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DSG3	NM_001944.3	c.216+44T>C		intron_variant		ENST00000257189.5	NP_001935.2
DSG3	XM_011525850.3	c.216+44T>C		intron_variant			XP_011524152.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DSG3	ENST00000257189.5	c.216+44T>C		intron_variant		1	NM_001944.3	ENSP00000257189.4

Frequencies

GnomAD3 genomes AF: 0.104 AC: 15781 AN: 151958 Hom.: 909 Cov.: 32

Gnomad AFR AF: 0.115

Gnomad AMI AF: 0.0713

Gnomad AMR AF: 0.0847

Gnomad ASJ AF: 0.0937

Gnomad EAS AF: 0.0917

Gnomad SAS AF: 0.111

Gnomad FIN AF: 0.103

Gnomad MID AF: 0.0955

Gnomad NFE AF: 0.103

Gnomad OTH AF: 0.0972

GnomAD3 exomes AF: 0.104 AC: 22877 AN: 219562 Hom.: 1258 AF XY: 0.106 AC XY: 12707 AN XY: 119684

Gnomad AFR exome AF: 0.121

Gnomad AMR exome AF: 0.0596

Gnomad ASJ exome AF: 0.112

Gnomad EAS exome AF: 0.0954

Gnomad SAS exome AF: 0.118

Gnomad FIN exome AF: 0.111

Gnomad NFE exome AF: 0.109

Gnomad OTH exome AF: 0.104

GnomAD4 exome AF: 0.102 AC: 145160 AN: 1417628 Hom.: 7664 Cov.: 27 AF XY: 0.103 AC XY: 72581 AN XY: 703830

Gnomad4 AFR exome AF: 0.117

Gnomad4 AMR exome AF: 0.0641

Gnomad4 ASJ exome AF: 0.104

Gnomad4 EAS exome AF: 0.107

Gnomad4 SAS exome AF: 0.117

Gnomad4 FIN exome AF: 0.114

Gnomad4 NFE exome AF: 0.102

Gnomad4 OTH exome AF: 0.100

GnomAD4 genome AF: 0.104 AC: 15790 AN: 152076 Hom.: 910 Cov.: 32 AF XY: 0.103 AC XY: 7653 AN XY: 74340

Gnomad4 AFR AF: 0.114

Gnomad4 AMR AF: 0.0846

Gnomad4 ASJ AF: 0.0937

Gnomad4 EAS AF: 0.0917

Gnomad4 SAS AF: 0.112

Gnomad4 FIN AF: 0.103

Gnomad4 NFE AF: 0.103

Gnomad4 OTH AF: 0.0986

Alfa AF: 0.102 Hom.: 805

Bravo AF: 0.102

Asia WGS AF: 0.131 AC: 454 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	Nov 11, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	2.3
DANN	Benign	0.67

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: rs17660414; hg19: chr18-29037131;