16-87604287-CCTGCTGCTGCTGCTGCTGCTGCTGCTGCTG-CCTGCTGCTGCTG

Variant names:

• chr16-87604287-CCTGCTGCTGCTGCTGCTG-C
• rs71156237
• ENST00000301008.5:n.715_732delCTGCTGCTGCTGCTGCTG

Variant summary

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

The ENST00000301008.5(JPH3):​n.715_732delCTGCTGCTGCTGCTGCTG 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 0.00118 in 1,432,806 control chromosomes in the GnomAD database, including 11 homozygotes. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0059 (7 hom., cov: 0)
  • Exomes 𝑓: 0.00062 (4 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 = 0.00594 (892/150066) while in subpopulation AFR AF = 0.0196 (797/40668). AF 95% confidence interval is 0.0185. There are 7 homozygotes in GnomAd4. There are 426 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.
• BS2: High AC in GnomAd4 at 892 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
JPH3	NM_020655.4	c.382+784_382+801delCTGCTGCTGCTGCTGCTG		intron_variant	Intron 1 of 4	ENST00000284262.3	NP_065706.2
JPH3	NM_001271604.4	c.455_472delCTGCTGCTGCTGCTGCTG	p.Ala152_Ala157del	disruptive_inframe_deletion	Exon 2 of 2		NP_001258533.1
JPH3	NM_001271605.3	c.*153_*170delCTGCTGCTGCTGCTGCTG		3_prime_UTR_variant	Exon 2 of 2		NP_001258534.1
JPH3	NR_073379.3	n.96+2382_96+2399delCTGCTGCTGCTGCTGCTG		intron_variant	Intron 1 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
JPH3	ENST00000301008.5	n.715_732delCTGCTGCTGCTGCTGCTG		non_coding_transcript_exon_variant	Exon 2 of 2	1
JPH3	ENST00000284262.3	c.382+784_382+801delCTGCTGCTGCTGCTGCTG		intron_variant	Intron 1 of 4	1	NM_020655.4	ENSP00000284262.2
JPH3	ENST00000537256.5	n.96+2382_96+2399delCTGCTGCTGCTGCTGCTG		intron_variant	Intron 1 of 5	2

Frequencies

GnomAD3 genomes AF: 0.00594 AC: 890 AN: 149958 Hom.: 7 Cov.: 0

Gnomad AFR AF: 0.0196

Gnomad AMI AF: 0.00111

Gnomad AMR AF: 0.00403

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000394

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000971

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.000237

Gnomad OTH AF: 0.00633

GnomAD4 exome AF: 0.000619 AC: 794 AN: 1282740 Hom.: 4 AF XY: 0.000558 AC XY: 353 AN XY: 632954

African (AFR) AF: 0.0174 AC: 493 AN: 28276

American (AMR) AF: 0.00142 AC: 46 AN: 32374

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21656

East Asian (EAS) AF: 0.000166 AC: 4 AN: 24078

South Asian (SAS) AF: 0.000360 AC: 28 AN: 77822

European-Finnish (FIN) AF: 0.000170 AC: 5 AN: 29386

Middle Eastern (MID) AF: 0.00237 AC: 12 AN: 5062

European-Non Finnish (NFE) AF: 0.000137 AC: 139 AN: 1013026

Other (OTH) AF: 0.00131 AC: 67 AN: 51060

GnomAD4 genome AF: 0.00594 AC: 892 AN: 150066 Hom.: 7 Cov.: 0 AF XY: 0.00582 AC XY: 426 AN XY: 73222

African (AFR) AF: 0.0196 AC: 797 AN: 40668

American (AMR) AF: 0.00403 AC: 61 AN: 15150

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

East Asian (EAS) AF: 0.000395 AC: 2 AN: 5062

South Asian (SAS) AF: 0.00 AC: 0 AN: 4710

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

Middle Eastern (MID) AF: 0.00342 AC: 1 AN: 292

European-Non Finnish (NFE) AF: 0.000237 AC: 16 AN: 67458

Other (OTH) AF: 0.00626 AC: 13 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;