17-41755432-C-A

Variant names:

• chr17-41755432-C-A
• rs552155645
• ENST00000310706.9:c.*15G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000310706.9(JUP):​c.*15G>T variant causes a splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: JUP ENST00000310706.9 splice_region
• Scores: Splicing: ADA: 0.6019
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.01
• Publications: 0 publications found

Genes affected

JUP (HGNC:6207): (junction plakoglobin) This gene encodes a major cytoplasmic protein which is the only known constituent common to submembranous plaques of both desmosomes and intermediate junctions. This protein forms distinct complexes with cadherins and desmosomal cadherins and is a member of the catenin family since it contains a distinct repeating amino acid motif called the armadillo repeat. Mutation in this gene has been associated with Naxos disease. Alternative splicing occurs in this gene; however, not all transcripts have been fully described. [provided by RefSeq, Jul 2008]

JUP Gene-Disease associations (from GenCC):

• arrhythmogenic right ventricular dysplasia 12

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• inherited epidermolysis bullosa

  Inheritance: AR Classification: STRONG Submitted by: Genomics England PanelApp
• Naxos disease

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Genomics England PanelApp, G2P, Orphanet, PanelApp Australia, Labcorp Genetics (formerly Invitae)
• lethal acantholytic epidermolysis bullosa

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
JUP	NM_002230.4	c.*312G>T		3_prime_UTR_variant	Exon 14 of 14	ENST00000393931.8	NP_002221.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
JUP	ENST00000393931.8	c.*312G>T		3_prime_UTR_variant	Exon 14 of 14	1	NM_002230.4	ENSP00000377508.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 263132 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 133628

African (AFR) AF: 0.00 AC: 0 AN: 7508

American (AMR) AF: 0.00 AC: 0 AN: 9418

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 9490

East Asian (EAS) AF: 0.00 AC: 0 AN: 23500

South Asian (SAS) AF: 0.00 AC: 0 AN: 5314

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 21602

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1346

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 167734

Other (OTH) AF: 0.00 AC: 0 AN: 17220

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	0.025
DANN	Benign	0.75
PhyloP100		1.0

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.60
dbscSNV1_RF	Benign	0.52
SpliceAI score (max)		0.62		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.62		Position offset: 0

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs552155645; hg19: chr17-39911684;