rs2562059

Positions:

• chr16-87605249-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020655.4(JPH3):​c.382+1721C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.501 in 152,098 control chromosomes in the GnomAD database, including 20,563 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 0.50 (20563 hom., cov: 32)
• Consequence: JPH3 NM_020655.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.83

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.684 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
JPH3	NM_020655.4	c.382+1721C>G		intron_variant		ENST00000284262.3	NP_065706.2
JPH3	NR_073379.3	n.96+3319C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
JPH3	ENST00000284262.3	c.382+1721C>G		intron_variant		1	NM_020655.4	ENSP00000284262.2
JPH3	ENST00000537256.5	n.96+3319C>G		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.501 AC: 76107 AN: 151978 Hom.: 20529 Cov.: 32

Gnomad AFR AF: 0.690

Gnomad AMI AF: 0.390

Gnomad AMR AF: 0.363

Gnomad ASJ AF: 0.427

Gnomad EAS AF: 0.129

Gnomad SAS AF: 0.390

Gnomad FIN AF: 0.516

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.456

Gnomad OTH AF: 0.495

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

GnomAD4 genome AF: 0.501 AC: 76189 AN: 152098 Hom.: 20563 Cov.: 32 AF XY: 0.496 AC XY: 36881 AN XY: 74344

Gnomad4 AFR AF: 0.691

Gnomad4 AMR AF: 0.362

Gnomad4 ASJ AF: 0.427

Gnomad4 EAS AF: 0.129

Gnomad4 SAS AF: 0.389

Gnomad4 FIN AF: 0.516

Gnomad4 NFE AF: 0.456

Gnomad4 OTH AF: 0.493

Alfa AF: 0.489 Hom.: 2348

Bravo AF: 0.493

Asia WGS AF: 0.302 AC: 1056 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.089
DANN	Benign	0.43

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

Publications

LitVar

Other links and lift over

dbSNP: rs2562059; hg19: chr16-87638855;