NM_020655.4:c.382+1721C>G

Variant names:

• chr16-87605249-C-G
• rs2562059
• NM_020655.4:c.382+1721C>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.684 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.382+1721C>G		intron	N/A	NP_065706.2
	JPH3	NR_073379.3		n.96+3319C>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.382+1721C>G		intron	N/A	ENSP00000284262.2	Q8WXH2-1
	JPH3	ENST00000537256.5	TSL:2	n.96+3319C>G		intron	N/A

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

African (AFR) AF: 0.691 AC: 28652 AN: 41482

American (AMR) AF: 0.362 AC: 5532 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.427 AC: 1480 AN: 3468

East Asian (EAS) AF: 0.129 AC: 669 AN: 5172

South Asian (SAS) AF: 0.389 AC: 1874 AN: 4814

European-Finnish (FIN) AF: 0.516 AC: 5463 AN: 10582

Middle Eastern (MID) AF: 0.503 AC: 148 AN: 294

European-Non Finnish (NFE) AF: 0.456 AC: 30976 AN: 67974

Other (OTH) AF: 0.493 AC: 1040 AN: 2108

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.089
DANN	Benign	0.43
PhyloP100		-2.8
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: rs2562059; hg19: chr16-87638855;