chr16-87604287-CCTG-C

Variant names:

• chr16-87604287-CCTG-C
• rs71156237
• ENST00000301008.5:n.730_732delCTG

Variant summary

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

The ENST00000301008.5(JPH3):​n.730_732delCTG 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 0.0101 in 1,389,866 control chromosomes in the GnomAD database, including 293 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.033 (232 hom., cov: 0)
  • Exomes 𝑓: 0.0074 (61 hom.)
• Consequence: JPH3 ENST00000301008.5 non_coding_transcript_exon
• Clinical Significance: 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-CCTG-C is Benign according to our data. Variant chr16-87604287-CCTG-C is described in ClinVar as Benign. ClinVar VariationId is 3911195.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.1 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000301008.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	JPH3	NM_020655.4	MANE Select	c.382+799_382+801delCTG		intron	N/A	NP_065706.2
	JPH3	NM_001271604.4		c.470_472delCTG	p.Ala157del	disruptive_inframe_deletion	Exon 2 of 2	NP_001258533.1
	JPH3	NM_001271605.3		c.*168_*170delCTG		3_prime_UTR	Exon 2 of 2	NP_001258534.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	JPH3	ENST00000301008.5	TSL:1	n.730_732delCTG		non_coding_transcript_exon	Exon 2 of 2
	JPH3	ENST00000284262.3	TSL:1 MANE Select	c.382+799_382+801delCTG		intron	N/A	ENSP00000284262.2
	JPH3	ENST00000537256.5	TSL:2	n.96+2397_96+2399delCTG		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0326 AC: 4883 AN: 149892 Hom.: 231 Cov.: 0

Gnomad AFR AF: 0.103

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0156

Gnomad ASJ AF: 0.0145

Gnomad EAS AF: 0.0252

Gnomad SAS AF: 0.00912

Gnomad FIN AF: 0.00165

Gnomad MID AF: 0.00955

Gnomad NFE AF: 0.00264

Gnomad OTH AF: 0.0287

GnomAD4 exome AF: 0.00738 AC: 9148 AN: 1239868 Hom.: 61 AF XY: 0.00723 AC XY: 4404 AN XY: 609046

African (AFR) AF: 0.0918 AC: 2540 AN: 27654

American (AMR) AF: 0.0175 AC: 516 AN: 29418

Ashkenazi Jewish (ASJ) AF: 0.0123 AC: 255 AN: 20734

East Asian (EAS) AF: 0.0241 AC: 524 AN: 21742

South Asian (SAS) AF: 0.0108 AC: 755 AN: 69586

European-Finnish (FIN) AF: 0.00420 AC: 118 AN: 28078

Middle Eastern (MID) AF: 0.00830 AC: 41 AN: 4938

European-Non Finnish (NFE) AF: 0.00383 AC: 3786 AN: 988486

Other (OTH) AF: 0.0125 AC: 613 AN: 49232

GnomAD4 genome AF: 0.0327 AC: 4898 AN: 149998 Hom.: 232 Cov.: 0 AF XY: 0.0321 AC XY: 2346 AN XY: 73192

African (AFR) AF: 0.103 AC: 4184 AN: 40646

American (AMR) AF: 0.0157 AC: 237 AN: 15140

Ashkenazi Jewish (ASJ) AF: 0.0145 AC: 50 AN: 3448

East Asian (EAS) AF: 0.0251 AC: 127 AN: 5062

South Asian (SAS) AF: 0.00934 AC: 44 AN: 4710

European-Finnish (FIN) AF: 0.00165 AC: 17 AN: 10284

Middle Eastern (MID) AF: 0.00685 AC: 2 AN: 292

European-Non Finnish (NFE) AF: 0.00264 AC: 178 AN: 67440

Other (OTH) AF: 0.0284 AC: 59 AN: 2076

Alfa AF: 0.0351 Hom.: 316

ClinVar

Significance: 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: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

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

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: rs71156237; hg19: chr16-87637893; COSMIC: COSV52464981; COSMIC: COSV52464981;