18-31467004-T-C

Variant names:

• chr18-31467004-T-C
• rs3794925
• NM_001944.3:c.1636+250T>C

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.1636+250T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.274 in 152,084 control chromosomes in the GnomAD database, including 5,832 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.27 (5832 hom., cov: 32)
• Consequence: DSG3 NM_001944.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.198

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=-0.83).
• BP6: Variant 18-31467004-T-C is Benign according to our data. Variant chr18-31467004-T-C is described in ClinVar as [Benign]. Clinvar id is 1250852.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.292 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DSG3	NM_001944.3	c.1636+250T>C		intron_variant	Intron 11 of 15	ENST00000257189.5	NP_001935.2
DSG3	XM_011525850.3	c.1636+250T>C		intron_variant	Intron 11 of 15		XP_011524152.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DSG3	ENST00000257189.5	c.1636+250T>C		intron_variant	Intron 11 of 15	1	NM_001944.3	ENSP00000257189.4

Frequencies

GnomAD3 genomes AF: 0.274 AC: 41650 AN: 151966 Hom.: 5828 Cov.: 32

Gnomad AFR AF: 0.281

Gnomad AMI AF: 0.340

Gnomad AMR AF: 0.226

Gnomad ASJ AF: 0.227

Gnomad EAS AF: 0.0732

Gnomad SAS AF: 0.243

Gnomad FIN AF: 0.300

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.296

Gnomad OTH AF: 0.275

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.274 AC: 41676 AN: 152084 Hom.: 5832 Cov.: 32 AF XY: 0.271 AC XY: 20184 AN XY: 74346

Gnomad4 AFR AF: 0.281

Gnomad4 AMR AF: 0.225

Gnomad4 ASJ AF: 0.227

Gnomad4 EAS AF: 0.0732

Gnomad4 SAS AF: 0.243

Gnomad4 FIN AF: 0.300

Gnomad4 NFE AF: 0.296

Gnomad4 OTH AF: 0.274

Alfa AF: 0.283 Hom.: 7139

Bravo AF: 0.265

Asia WGS AF: 0.172 AC: 601 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Nov 11, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.9
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: rs3794925; hg19: chr18-29046967;