16-87604287-CCTGCTGCTGCTGCTGCTGCTGCTGCTGCTG-CCTGCTGCTGCTGCTGCTGCTGCTG

Variant names:

• chr16-87604287-CCTGCTG-C
• rs71156237
• ENST00000301008.5:n.727_732delCTGCTG

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1 BS2

The ENST00000301008.5(JPH3):​n.727_732delCTGCTG variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00164 in 1,432,648 control chromosomes in the GnomAD database, including 12 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0067 (9 hom., cov: 0)
  • Exomes 𝑓: 0.0010 (3 hom.)
• Consequence: JPH3 ENST00000301008.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• 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 -8 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00672 (1008/150060) while in subpopulation AFR AF = 0.0219 (890/40662). AF 95% confidence interval is 0.0207. There are 9 homozygotes in GnomAd4. There are 475 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1008 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
JPH3	NM_020655.4	c.382+796_382+801delCTGCTG		intron_variant	Intron 1 of 4	ENST00000284262.3	NP_065706.2
JPH3	NM_001271604.4	c.467_472delCTGCTG	p.Ala156_Ala157del	disruptive_inframe_deletion	Exon 2 of 2		NP_001258533.1
JPH3	NM_001271605.3	c.*165_*170delCTGCTG		3_prime_UTR_variant	Exon 2 of 2		NP_001258534.1
JPH3	NR_073379.3	n.96+2394_96+2399delCTGCTG		intron_variant	Intron 1 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
JPH3	ENST00000301008.5	n.727_732delCTGCTG		non_coding_transcript_exon_variant	Exon 2 of 2	1
JPH3	ENST00000284262.3	c.382+796_382+801delCTGCTG		intron_variant	Intron 1 of 4	1	NM_020655.4	ENSP00000284262.2
JPH3	ENST00000537256.5	n.96+2394_96+2399delCTGCTG		intron_variant	Intron 1 of 5	2

Frequencies

GnomAD3 genomes AF: 0.00668 AC: 1002 AN: 149952 Hom.: 9 Cov.: 0

Gnomad AFR AF: 0.0218

Gnomad AMI AF: 0.00889

Gnomad AMR AF: 0.00258

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000591

Gnomad SAS AF: 0.00276

Gnomad FIN AF: 0.0000971

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000593

Gnomad OTH AF: 0.00633

GnomAD4 exome AF: 0.00104 AC: 1339 AN: 1282588 Hom.: 3 AF XY: 0.00102 AC XY: 644 AN XY: 632894

African (AFR) AF: 0.0178 AC: 500 AN: 28164

American (AMR) AF: 0.00136 AC: 44 AN: 32392

Ashkenazi Jewish (ASJ) AF: 0.0000462 AC: 1 AN: 21656

East Asian (EAS) AF: 0.000166 AC: 4 AN: 24070

South Asian (SAS) AF: 0.00220 AC: 171 AN: 77820

European-Finnish (FIN) AF: 0.000136 AC: 4 AN: 29380

Middle Eastern (MID) AF: 0.00356 AC: 18 AN: 5060

European-Non Finnish (NFE) AF: 0.000495 AC: 501 AN: 1012982

Other (OTH) AF: 0.00188 AC: 96 AN: 51064

GnomAD4 genome AF: 0.00672 AC: 1008 AN: 150060 Hom.: 9 Cov.: 0 AF XY: 0.00649 AC XY: 475 AN XY: 73218

African (AFR) AF: 0.0219 AC: 890 AN: 40662

American (AMR) AF: 0.00257 AC: 39 AN: 15150

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3448

East Asian (EAS) AF: 0.000593 AC: 3 AN: 5062

South Asian (SAS) AF: 0.00255 AC: 12 AN: 4710

European-Finnish (FIN) AF: 0.0000971 AC: 1 AN: 10302

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.000593 AC: 40 AN: 67458

Other (OTH) AF: 0.00723 AC: 15 AN: 2076

Alfa AF: 0.00 Hom.: 316

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

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; COSMIC: COSV52471734; COSMIC: COSV52471734;