NM_001944.3:c.217-285A>C

Variant names:

• chr18-31458160-A-C
• rs1941184
• NM_001944.3:c.217-285A>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001944.3(DSG3):​c.217-285A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.379 in 151,892 control chromosomes in the GnomAD database, including 11,779 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.38 (11779 hom., cov: 32)
• Consequence: DSG3 NM_001944.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.29
• Publications: 14 publications found

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 Gene-Disease associations (from GenCC):

• blistering, acantholytic, of oral and laryngeal mucosa

  Inheritance: Unknown, AR Classification: MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 18-31458160-A-C is Benign according to our data. Variant chr18-31458160-A-C is described in ClinVar as Benign. ClinVar VariationId is 1285963.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.541 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001944.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DSG3	NM_001944.3	MANE Select	c.217-285A>C		intron	N/A	NP_001935.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DSG3	ENST00000257189.5	TSL:1 MANE Select	c.217-285A>C		intron	N/A	ENSP00000257189.4

Frequencies

GnomAD3 genomes AF: 0.379 AC: 57508 AN: 151774 Hom.: 11736 Cov.: 32

Gnomad AFR AF: 0.546

Gnomad AMI AF: 0.205

Gnomad AMR AF: 0.286

Gnomad ASJ AF: 0.303

Gnomad EAS AF: 0.252

Gnomad SAS AF: 0.471

Gnomad FIN AF: 0.374

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.310

Gnomad OTH AF: 0.338

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

GnomAD4 genome AF: 0.379 AC: 57610 AN: 151892 Hom.: 11779 Cov.: 32 AF XY: 0.380 AC XY: 28221 AN XY: 74272

African (AFR) AF: 0.547 AC: 22644 AN: 41426

American (AMR) AF: 0.287 AC: 4375 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.303 AC: 1050 AN: 3462

East Asian (EAS) AF: 0.252 AC: 1299 AN: 5158

South Asian (SAS) AF: 0.471 AC: 2269 AN: 4818

European-Finnish (FIN) AF: 0.374 AC: 3937 AN: 10530

Middle Eastern (MID) AF: 0.262 AC: 77 AN: 294

European-Non Finnish (NFE) AF: 0.310 AC: 21059 AN: 67922

Other (OTH) AF: 0.338 AC: 713 AN: 2108

Alfa AF: 0.332 Hom.: 31039

Bravo AF: 0.375

Asia WGS AF: 0.370 AC: 1285 AN: 3476

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.15
DANN	Benign	0.44
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1941184; hg19: chr18-29038123; COSMIC: COSV57124488;