rs782166986

Variant names:

• chr17-41755074-C-A
• rs782166986
• NM_002230.4:c.*670G>T

Your query was ambiguous. Multiple possible variants found:

• chr17-41755074-C-A
• chr17-41755074-C-G
• chr17-41755074-C-T

Variant summary

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

The NM_002230.4(JUP):​c.*670G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000335 in 387,902 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000038 (0 hom.)
• Consequence: JUP NM_002230.4 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:2
• Conservation: PhyloP100: -3.38
• 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=-0.87).

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.*670G>T		3_prime_UTR	Exon 14 of 14	NP_002221.1	P14923
	JUP	NM_001352773.2		c.*670G>T		3_prime_UTR	Exon 14 of 14	NP_001339702.1	P14923
	JUP	NM_001352774.2		c.*373G>T		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.*670G>T		3_prime_UTR	Exon 14 of 14	ENSP00000377508.3	P14923
	JUP	ENST00000310706.9	TSL:1	c.*373G>T		3_prime_UTR	Exon 15 of 15	ENSP00000311113.5	P14923
	JUP	ENST00000393930.5	TSL:5	c.*373G>T		3_prime_UTR	Exon 15 of 15	ENSP00000377507.1	P14923

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 152030 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000382 AC: 9 AN: 235872 Hom.: 0 Cov.: 0 AF XY: 0.0000334 AC XY: 4 AN XY: 119644

African (AFR) AF: 0.00 AC: 0 AN: 6970

American (AMR) AF: 0.00 AC: 0 AN: 7056

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 8936

East Asian (EAS) AF: 0.00 AC: 0 AN: 22144

South Asian (SAS) AF: 0.00 AC: 0 AN: 2080

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 19970

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1236

European-Non Finnish (NFE) AF: 0.0000527 AC: 8 AN: 151744

Other (OTH) AF: 0.0000635 AC: 1 AN: 15736

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 152030 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74262

African (AFR) AF: 0.0000242 AC: 1 AN: 41386

American (AMR) AF: 0.00 AC: 0 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10600

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68002

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000416

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	-0.87
CADD	Benign	0.044
DANN	Benign	0.41
PhyloP100		-3.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs782166986; hg19: chr17-39911326;