16-87604287-CCTGCTGCTGCTGCTGCTGCTGCTGCTGCTG-CCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTG

Variant names:

• chr16-87604287-C-CCTGCTGCTG
• rs71156237
• ENST00000301008.5:n.724_732dupCTGCTGCTG

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The ENST00000301008.5(JPH3):​n.724_732dupCTGCTGCTG variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.071 (427 hom., cov: 0)
  • Exomes 𝑓: 0.071 (2004 hom.)
  • Failed GnomAD Quality Control
• Consequence: JPH3 ENST00000301008.5 non_coding_transcript_exon
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.966
• Publications: 1 publications found

Genes affected

JPH3 (HGNC:14203): (junctophilin 3) Junctional complexes between the plasma membrane and endoplasmic/sarcoplasmic reticulum are a common feature of all excitable cell types and mediate cross talk between cell surface and intracellular ion channels. The protein encoded by this gene is a component of junctional complexes and is composed of a C-terminal hydrophobic segment spanning the endoplasmic/sarcoplasmic reticulum membrane and a remaining cytoplasmic domain that shows specific affinity for the plasma membrane. CAG/CTG repeat expansion from normally 6-28 repeats to 40-59 repeats in the 3' UTR of this gene have been associated with Huntington disease-like 2 (HDL2). This gene is a member of the junctophilin gene family. Alternatively spliced transcript variants have been described for this gene. [provided by RefSeq, Jul 2016]

JPH3 Gene-Disease associations (from GenCC):

• Huntington disease-like 2

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 16-87604287-C-CCTGCTGCTG is Benign according to our data. Variant chr16-87604287-C-CCTGCTGCTG is described in ClinVar as [Likely_benign]. Clinvar id is 3911193.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0887 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
JPH3	NM_020655.4	c.382+793_382+801dupCTGCTGCTG		intron_variant	Intron 1 of 4	ENST00000284262.3	NP_065706.2
JPH3	NM_001271604.4	c.464_472dupCTGCTGCTG	p.Ala155_Ala157dup	disruptive_inframe_insertion	Exon 2 of 2		NP_001258533.1
JPH3	NM_001271605.3	c.*162_*170dupCTGCTGCTG		3_prime_UTR_variant	Exon 2 of 2		NP_001258534.1
JPH3	NR_073379.3	n.96+2391_96+2399dupCTGCTGCTG		intron_variant	Intron 1 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
JPH3	ENST00000301008.5	n.724_732dupCTGCTGCTG		non_coding_transcript_exon_variant	Exon 2 of 2	1
JPH3	ENST00000284262.3	c.382+793_382+801dupCTGCTGCTG		intron_variant	Intron 1 of 4	1	NM_020655.4	ENSP00000284262.2
JPH3	ENST00000537256.5	n.96+2391_96+2399dupCTGCTGCTG		intron_variant	Intron 1 of 5	2

Frequencies

GnomAD3 genomes AF: 0.0715 AC: 10713 AN: 149916 Hom.: 428 Cov.: 0

Gnomad AFR AF: 0.0914

Gnomad AMI AF: 0.0711

Gnomad AMR AF: 0.0519

Gnomad ASJ AF: 0.0467

Gnomad EAS AF: 0.0207

Gnomad SAS AF: 0.0305

Gnomad FIN AF: 0.0800

Gnomad MID AF: 0.0510

Gnomad NFE AF: 0.0708

Gnomad OTH AF: 0.0668

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0711 AC: 91046 AN: 1280580 Hom.: 2004 Cov.: 30 AF XY: 0.0699 AC XY: 44180 AN XY: 631964

African (AFR) AF: 0.0985 AC: 2776 AN: 28178

American (AMR) AF: 0.0457 AC: 1481 AN: 32390

Ashkenazi Jewish (ASJ) AF: 0.0469 AC: 1015 AN: 21628

East Asian (EAS) AF: 0.0372 AC: 895 AN: 24058

South Asian (SAS) AF: 0.0336 AC: 2616 AN: 77804

European-Finnish (FIN) AF: 0.0854 AC: 2509 AN: 29370

Middle Eastern (MID) AF: 0.0401 AC: 203 AN: 5060

European-Non Finnish (NFE) AF: 0.0752 AC: 76046 AN: 1011118

Other (OTH) AF: 0.0688 AC: 3505 AN: 50974

GnomAD4 genome AF: 0.0714 AC: 10707 AN: 150024 Hom.: 427 Cov.: 0 AF XY: 0.0690 AC XY: 5051 AN XY: 73202

African (AFR) AF: 0.0912 AC: 3707 AN: 40648

American (AMR) AF: 0.0518 AC: 784 AN: 15148

Ashkenazi Jewish (ASJ) AF: 0.0467 AC: 161 AN: 3446

East Asian (EAS) AF: 0.0205 AC: 104 AN: 5062

South Asian (SAS) AF: 0.0304 AC: 143 AN: 4710

European-Finnish (FIN) AF: 0.0800 AC: 824 AN: 10296

Middle Eastern (MID) AF: 0.0411 AC: 12 AN: 292

European-Non Finnish (NFE) AF: 0.0707 AC: 4771 AN: 67448

Other (OTH) AF: 0.0661 AC: 137 AN: 2074

Alfa AF: 0.0422 Hom.: 316

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Feb 16, 2025

Laboratory of Genetics, Children's Clinical University Hospital Latvia

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.97
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs71156237; hg19: chr16-87637893;