rs17836505

Variant names:

• chr16-87688085-A-G
• rs17836505
• NM_020655.4:c.1286-1561A>G

Your query was ambiguous. Multiple possible variants found:

• chr16-87688085-A-G
• chr16-87688085-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020655.4(JPH3):​c.1286-1561A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.51 in 152,036 control chromosomes in the GnomAD database, including 19,863 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.51 (19863 hom., cov: 32)
• Consequence: JPH3 NM_020655.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.592
• Publications: 7 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.566 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020655.4. 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
	JPH3	NM_020655.4	MANE Select	c.1286-1561A>G		intron	N/A	NP_065706.2
	JPH3	NR_073379.3		n.1000-1561A>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	JPH3	ENST00000284262.3	TSL:1 MANE Select	c.1286-1561A>G		intron	N/A	ENSP00000284262.2	Q8WXH2-1
	JPH3	ENST00000537256.5	TSL:2	n.1000-1561A>G		intron	N/A
	JPH3	ENST00000563609.1	TSL:2	n.1580-1561A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.510 AC: 77459 AN: 151918 Hom.: 19832 Cov.: 32

Gnomad AFR AF: 0.572

Gnomad AMI AF: 0.474

Gnomad AMR AF: 0.523

Gnomad ASJ AF: 0.605

Gnomad EAS AF: 0.403

Gnomad SAS AF: 0.555

Gnomad FIN AF: 0.428

Gnomad MID AF: 0.630

Gnomad NFE AF: 0.482

Gnomad OTH AF: 0.518

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.510 AC: 77552 AN: 152036 Hom.: 19863 Cov.: 32 AF XY: 0.506 AC XY: 37626 AN XY: 74308

African (AFR) AF: 0.572 AC: 23747 AN: 41484

American (AMR) AF: 0.523 AC: 7994 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.605 AC: 2100 AN: 3470

East Asian (EAS) AF: 0.402 AC: 2076 AN: 5158

South Asian (SAS) AF: 0.555 AC: 2668 AN: 4808

European-Finnish (FIN) AF: 0.428 AC: 4534 AN: 10582

Middle Eastern (MID) AF: 0.629 AC: 185 AN: 294

European-Non Finnish (NFE) AF: 0.482 AC: 32725 AN: 67934

Other (OTH) AF: 0.519 AC: 1092 AN: 2104

Alfa AF: 0.499 Hom.: 28598

Bravo AF: 0.516

Asia WGS AF: 0.515 AC: 1789 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.063
DANN	Benign	0.34
PhyloP100		-0.59
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: rs17836505; hg19: chr16-87721691;