chr18-31448221-C-G

Position:

• chr18-31448221-C-G

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.48+296C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.282 in 152,046 control chromosomes in the GnomAD database, including 6,964 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.28 (6964 hom., cov: 33)
• Consequence: DSG3 NM_001944.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.160

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=-0.74).
• BP6: Variant 18-31448221-C-G is Benign according to our data. Variant chr18-31448221-C-G is described in ClinVar as [Benign]. Clinvar id is 1174288.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.451 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DSG3	NM_001944.3	c.48+296C>G		intron_variant		ENST00000257189.5	NP_001935.2
DSG3	XM_011525850.3	c.48+296C>G		intron_variant			XP_011524152.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DSG3	ENST00000257189.5	c.48+296C>G		intron_variant		1	NM_001944.3	ENSP00000257189	P1

Frequencies

GnomAD3 genomes AF: 0.282 AC: 42805 AN: 151928 Hom.: 6942 Cov.: 33

Gnomad AFR AF: 0.456

Gnomad AMI AF: 0.134

Gnomad AMR AF: 0.203

Gnomad ASJ AF: 0.211

Gnomad EAS AF: 0.146

Gnomad SAS AF: 0.360

Gnomad FIN AF: 0.276

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.206

Gnomad OTH AF: 0.247

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

GnomAD4 genome AF: 0.282 AC: 42879 AN: 152046 Hom.: 6964 Cov.: 33 AF XY: 0.284 AC XY: 21086 AN XY: 74320

Gnomad4 AFR AF: 0.456

Gnomad4 AMR AF: 0.203

Gnomad4 ASJ AF: 0.211

Gnomad4 EAS AF: 0.145

Gnomad4 SAS AF: 0.360

Gnomad4 FIN AF: 0.276

Gnomad4 NFE AF: 0.207

Gnomad4 OTH AF: 0.246

Alfa AF: 0.244 Hom.: 612

Bravo AF: 0.282

Asia WGS AF: 0.232 AC: 808 AN: 3470

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

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	-0.74
CADD	Benign	9.0
DANN	Benign	0.80

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: rs8089502; hg19: chr18-29028184;