Variant chr18-31447808-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001944.3(DSG3):c.-70C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.215 in 1,357,810 control chromosomes in the GnomAD database, including 35,187 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.27 ( 6677 hom., cov: 32)

Exomes 𝑓: 0.21 ( 28510 hom. )

Consequence

DSG3
NM_001944.3 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.474

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 18-31447808-C-T is Benign according to our data. Variant chr18-31447808-C-T is described in ClinVar as [Benign]. Clinvar id is 1183480.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.449 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DSG3	NM_001944.3 linkuse as main transcript	c.-70C>T		5_prime_UTR_variant	1/16	ENST00000257189.5	NP_001935.2	P32926
DSG3	XM_011525850.3 linkuse as main transcript	c.-70C>T		5_prime_UTR_variant	1/16		XP_011524152.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DSG3	ENST00000257189 linkuse as main transcript	c.-70C>T		5_prime_UTR_variant	1/16	1	NM_001944.3	ENSP00000257189.4		P32926

Frequencies

GnomAD3 genomes

AF:

0.273

AC:

41498

AN:

151934

Hom.:

6654

Cov.:

show subpopulations

Gnomad AFR

AF:

0.454

Gnomad AMI

AF:

0.130

Gnomad AMR

AF:

0.193

Gnomad ASJ

AF:

0.205

Gnomad EAS

AF:

0.145

Gnomad SAS

AF:

0.344

Gnomad FIN

AF:

0.258

Gnomad MID

AF:

0.143

Gnomad NFE

AF:

0.195

Gnomad OTH

AF:

0.238

GnomAD4 exome

AF:

0.208

AC:

250838

AN:

1205756

Hom.:

28510

Cov.:

AF XY:

0.212

AC XY:

128345

AN XY:

606140

show subpopulations

Gnomad4 AFR exome

AF:

0.463

Gnomad4 AMR exome

AF:

0.211

Gnomad4 ASJ exome

AF:

0.204

Gnomad4 EAS exome

AF:

0.127

Gnomad4 SAS exome

AF:

0.346

Gnomad4 FIN exome

AF:

0.244

Gnomad4 NFE exome

AF:

0.191

Gnomad4 OTH exome

AF:

0.215

GnomAD4 genome

AF:

0.273

AC:

41576

AN:

152054

Hom.:

6677

Cov.:

AF XY:

0.275

AC XY:

20400

AN XY:

74314

show subpopulations

Gnomad4 AFR

AF:

0.454

Gnomad4 AMR

AF:

0.194

Gnomad4 ASJ

AF:

0.205

Gnomad4 EAS

AF:

0.144

Gnomad4 SAS

AF:

0.345

Gnomad4 FIN

AF:

0.258

Gnomad4 NFE

AF:

0.195

Gnomad4 OTH

AF:

0.237

Alfa

AF:

0.231

Hom.:

1886

Bravo

AF:

0.274

Asia WGS

AF:

0.227

AC:

793

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

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

-0.80

CADD

Benign

5.2

DANN

Benign

0.74

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over