chr16-87688085-A-G

Position:

• chr16-87688085-A-G

Variant summary

Our verdict is Benign. Variant got -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

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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.566 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
JPH3	NM_020655.4	c.1286-1561A>G		intron_variant		ENST00000284262.3	NP_065706.2
JPH3	NR_073379.3	n.1000-1561A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
JPH3	ENST00000284262.3	c.1286-1561A>G		intron_variant		1	NM_020655.4	ENSP00000284262.2
JPH3	ENST00000537256.5	n.1000-1561A>G		intron_variant		2
JPH3	ENST00000563609.1	n.1580-1561A>G		intron_variant		2

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

Gnomad4 AFR AF: 0.572

Gnomad4 AMR AF: 0.523

Gnomad4 ASJ AF: 0.605

Gnomad4 EAS AF: 0.402

Gnomad4 SAS AF: 0.555

Gnomad4 FIN AF: 0.428

Gnomad4 NFE AF: 0.482

Gnomad4 OTH AF: 0.519

Alfa AF: 0.496 Hom.: 19384

Bravo AF: 0.516

Asia WGS AF: 0.515 AC: 1789 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.063
DANN	Benign	0.34

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: rs17836505; hg19: chr16-87721691;