Variant 18-31458573-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001944.3(DSG3):c.345C>T(p.Val115=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0257 in 1,613,462 control chromosomes in the GnomAD database, including 1,746 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.068 ( 771 hom., cov: 32)

Exomes 𝑓: 0.021 ( 975 hom. )

Consequence

DSG3
NM_001944.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.46

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.51).

BP6

Variant 18-31458573-C-T is Benign according to our data. Variant chr18-31458573-C-T is described in ClinVar as [Benign]. Clinvar id is 1277439.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.46 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.19 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.345C>T	p.Val115=	synonymous_variant	4/16	ENST00000257189.5	NP_001935.2
DSG3	XM_011525850.3 linkuse as main transcript	c.345C>T	p.Val115=	synonymous_variant	4/16		XP_011524152.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DSG3	ENST00000257189.5 linkuse as main transcript	c.345C>T	p.Val115=	synonymous_variant	4/16	1	NM_001944.3	ENSP00000257189	P1

Frequencies

GnomAD3 genomes

AF:

0.0675

AC:

10266

AN:

152038

Hom.:

769

Cov.:

show subpopulations

Gnomad AFR

AF:

0.193

Gnomad AMI

AF:

0.0197

Gnomad AMR

AF:

0.0296

Gnomad ASJ

AF:

0.00346

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00623

Gnomad FIN

AF:

0.0435

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.0176

Gnomad OTH

AF:

0.0531

GnomAD3 exomes

AF:

0.0299

AC:

7496

AN:

250868

Hom.:

384

AF XY:

0.0261

AC XY:

3540

AN XY:

135598

show subpopulations

Gnomad AFR exome

AF:

0.201

Gnomad AMR exome

AF:

0.0176

Gnomad ASJ exome

AF:

0.00536

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00648

Gnomad FIN exome

AF:

0.0450

Gnomad NFE exome

AF:

0.0199

Gnomad OTH exome

AF:

0.0236

GnomAD4 exome

AF:

0.0214

AC:

31240

AN:

1461306

Hom.:

975

Cov.:

AF XY:

0.0203

AC XY:

14744

AN XY:

726922

show subpopulations

Gnomad4 AFR exome

AF:

0.201

Gnomad4 AMR exome

AF:

0.0182

Gnomad4 ASJ exome

AF:

0.00387

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00656

Gnomad4 FIN exome

AF:

0.0430

Gnomad4 NFE exome

AF:

0.0169

Gnomad4 OTH exome

AF:

0.0278

GnomAD4 genome

AF:

0.0677

AC:

10294

AN:

152156

Hom.:

771

Cov.:

AF XY:

0.0659

AC XY:

4905

AN XY:

74380

show subpopulations

Gnomad4 AFR

AF:

0.193

Gnomad4 AMR

AF:

0.0295

Gnomad4 ASJ

AF:

0.00346

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00582

Gnomad4 FIN

AF:

0.0435

Gnomad4 NFE

AF:

0.0176

Gnomad4 OTH

AF:

0.0526

Alfa

AF:

0.0254

Hom.:

289

Bravo

AF:

0.0719

Asia WGS

AF:

0.0140

AC:

AN:

3478

EpiCase

AF:

0.0184

EpiControl

AF:

0.0186

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 09, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.51

CADD

Benign

1.6

DANN

Benign

0.61

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