chr18-31459320-G-A

Position:

• chr18-31459320-G-A

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.517+143G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0992 in 799,166 control chromosomes in the GnomAD database, including 4,311 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.10 (852 hom., cov: 32)
  • Exomes 𝑓: 0.099 (3459 hom.)
• Consequence: DSG3 NM_001944.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.514

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=-0.81).
• BP6: Variant 18-31459320-G-A is Benign according to our data. Variant chr18-31459320-G-A is described in ClinVar as [Benign]. Clinvar id is 1287909.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.105 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DSG3	NM_001944.3	c.517+143G>A		intron_variant		ENST00000257189.5	NP_001935.2
DSG3	XM_011525850.3	c.517+143G>A		intron_variant			XP_011524152.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DSG3	ENST00000257189.5	c.517+143G>A		intron_variant		1	NM_001944.3	ENSP00000257189	P1

Frequencies

GnomAD3 genomes AF: 0.101 AC: 15372 AN: 152028 Hom.: 852 Cov.: 32

Gnomad AFR AF: 0.105

Gnomad AMI AF: 0.0713

Gnomad AMR AF: 0.0846

Gnomad ASJ AF: 0.0937

Gnomad EAS AF: 0.0910

Gnomad SAS AF: 0.112

Gnomad FIN AF: 0.103

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.103

Gnomad OTH AF: 0.0960

GnomAD4 exome AF: 0.0988 AC: 63936 AN: 647020 Hom.: 3459 AF XY: 0.0996 AC XY: 33055 AN XY: 331914

Gnomad4 AFR exome AF: 0.102

Gnomad4 AMR exome AF: 0.0742

Gnomad4 ASJ exome AF: 0.0994

Gnomad4 EAS exome AF: 0.108

Gnomad4 SAS exome AF: 0.115

Gnomad4 FIN exome AF: 0.111

Gnomad4 NFE exome AF: 0.0967

Gnomad4 OTH exome AF: 0.0974

GnomAD4 genome AF: 0.101 AC: 15377 AN: 152146 Hom.: 852 Cov.: 32 AF XY: 0.100 AC XY: 7465 AN XY: 74398

Gnomad4 AFR AF: 0.105

Gnomad4 AMR AF: 0.0845

Gnomad4 ASJ AF: 0.0937

Gnomad4 EAS AF: 0.0911

Gnomad4 SAS AF: 0.113

Gnomad4 FIN AF: 0.103

Gnomad4 NFE AF: 0.103

Gnomad4 OTH AF: 0.0974

Alfa AF: 0.104 Hom.: 103

Bravo AF: 0.0987

Asia WGS AF: 0.129 AC: 447 AN: 3476

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

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.2
DANN	Benign	0.57

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: rs2276105; hg19: chr18-29039283;