chr17-41754957-T-C

Variant names:

• chr17-41754957-T-C
• rs551870163
• NM_002230.4:c.*787A>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_002230.4(JUP):​c.*787A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00113 in 203,042 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0012 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00096 (1 hom.)
• Consequence: JUP NM_002230.4 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:2
• Conservation: PhyloP100: -2.56
• 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 cardiomyopathy

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• 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, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Genomics England PanelApp, Orphanet
• lethal acantholytic epidermolysis bullosa

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002230.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	JUP	NM_002230.4	MANE Select	c.*787A>G		3_prime_UTR	Exon 14 of 14	NP_002221.1	P14923
	JUP	NM_001352773.2		c.*787A>G		3_prime_UTR	Exon 14 of 14	NP_001339702.1	P14923
	JUP	NM_001352774.2		c.*490A>G		3_prime_UTR	Exon 15 of 15	NP_001339703.1	P14923

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	JUP	ENST00000393931.8	TSL:1 MANE Select	c.*787A>G		3_prime_UTR	Exon 14 of 14	ENSP00000377508.3	P14923
	JUP	ENST00000310706.9	TSL:1	c.*490A>G		3_prime_UTR	Exon 15 of 15	ENSP00000311113.5	P14923
	JUP	ENST00000393930.5	TSL:5	c.*490A>G		3_prime_UTR	Exon 15 of 15	ENSP00000377507.1	P14923

Frequencies

GnomAD3 genomes AF: 0.00119 AC: 181 AN: 152080 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.000194

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0157

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.000478

GnomAD4 exome AF: 0.000964 AC: 49 AN: 50844 Hom.: 1 Cov.: 0 AF XY: 0.00102 AC XY: 26 AN XY: 25434

African (AFR) AF: 0.00 AC: 0 AN: 1990

American (AMR) AF: 0.00 AC: 0 AN: 1462

Ashkenazi Jewish (ASJ) AF: 0.000462 AC: 1 AN: 2164

East Asian (EAS) AF: 0.00 AC: 0 AN: 4314

South Asian (SAS) AF: 0.00 AC: 0 AN: 428

European-Finnish (FIN) AF: 0.0159 AC: 46 AN: 2900

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 284

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 33798

Other (OTH) AF: 0.000571 AC: 2 AN: 3504

GnomAD4 genome AF: 0.00119 AC: 181 AN: 152198 Hom.: 1 Cov.: 32 AF XY: 0.00180 AC XY: 134 AN XY: 74410

African (AFR) AF: 0.00 AC: 0 AN: 41542

American (AMR) AF: 0.00 AC: 0 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00115 AC: 4 AN: 3466

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5152

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.0157 AC: 167 AN: 10604

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000118 AC: 8 AN: 67998

Other (OTH) AF: 0.000473 AC: 1 AN: 2112

Alfa AF: 0.000212 Hom.: 0

Bravo AF: 0.0000529

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Arrhythmogenic right ventricular dysplasia 12 (1)
-	1	-	Naxos disease (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.32
DANN	Benign	0.58
PhyloP100		-2.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs551870163; hg19: chr17-39911209;