Variant 18-31456353-A-G 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.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

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.0100

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 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_multiple_submitters_no_conflicts, 2 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	Protein	UniProt
DSG3	NM_001944.3 linkuse as main transcript	c.49-87A>G		intron_variant		ENST00000257189.5	NP_001935.2
DSG3	XM_011525850.3 linkuse as main transcript	c.49-87A>G		intron_variant			XP_011524152.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DSG3	ENST00000257189.5 linkuse as main transcript	c.49-87A>G		intron_variant		1	NM_001944.3	ENSP00000257189	P1

Frequencies

GnomAD3 genomes

AF:

0.278

AC:

42267

AN:

151964

Hom.:

6663

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.281

AC XY:

20872

AN XY:

74358

show subpopulations

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: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	Jun 19, 2021	- -

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

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