Variant 16-87644970-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_ModerateBP7BS1BS2

The NM_020655.4(JPH3):c.1095C>T(p.Arg365Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0301 in 1,610,588 control chromosomes in the GnomAD database, including 902 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 0.023 ( 59 hom., cov: 32)

Exomes 𝑓: 0.031 ( 843 hom. )

Consequence

JPH3
NM_020655.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.254

Variant links:

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 links:

JPH3 (HGNC:):

JPH3 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.4).

BP7

Synonymous conserved (PhyloP=-0.254 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0231 (3508/152182) while in subpopulation NFE AF= 0.031 (2108/67994). AF 95% confidence interval is 0.0299. There are 59 homozygotes in gnomad4. There are 1617 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 3508 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
JPH3	NM_020655.4 linkuse as main transcript	c.1095C>T	p.Arg365Arg	synonymous_variant	2/5	ENST00000284262.3	NP_065706.2	Q8WXH2-1B4DIC1F8W9A3
JPH3	NR_073379.3 linkuse as main transcript	n.809C>T		non_coding_transcript_exon_variant	2/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
JPH3	ENST00000284262.3 linkuse as main transcript	c.1095C>T	p.Arg365Arg	synonymous_variant	2/5	1	NM_020655.4	ENSP00000284262.2		Q8WXH2-1
JPH3	ENST00000537256.5 linkuse as main transcript	n.809C>T		non_coding_transcript_exon_variant	2/6	2

Frequencies

GnomAD3 genomes

AF:

0.0230

AC:

3503

AN:

152064

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0167

Gnomad AMI

AF:

0.0253

Gnomad AMR

AF:

0.0265

Gnomad ASJ

AF:

0.0343

Gnomad EAS

AF:

0.00155

Gnomad SAS

AF:

0.00808

Gnomad FIN

AF:

0.00585

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.0310

Gnomad OTH

AF:

0.0187

GnomAD3 exomes

AF:

0.0206

AC:

5025

AN:

243482

Hom.:

AF XY:

0.0209

AC XY:

2778

AN XY:

133030

show subpopulations

Gnomad AFR exome

AF:

0.0166

Gnomad AMR exome

AF:

0.0142

Gnomad ASJ exome

AF:

0.0336

Gnomad EAS exome

AF:

0.000843

Gnomad SAS exome

AF:

0.0119

Gnomad FIN exome

AF:

0.00519

Gnomad NFE exome

AF:

0.0301

Gnomad OTH exome

AF:

0.0237

GnomAD4 exome

AF:

0.0308

AC:

44923

AN:

1458406

Hom.:

843

Cov.:

AF XY:

0.0301

AC XY:

21807

AN XY:

725668

show subpopulations

Gnomad4 AFR exome

AF:

0.0145

Gnomad4 AMR exome

AF:

0.0144

Gnomad4 ASJ exome

AF:

0.0339

Gnomad4 EAS exome

AF:

0.000579

Gnomad4 SAS exome

AF:

0.0119

Gnomad4 FIN exome

AF:

0.00619

Gnomad4 NFE exome

AF:

0.0356

Gnomad4 OTH exome

AF:

0.0304

GnomAD4 genome

AF:

0.0231

AC:

3508

AN:

152182

Hom.:

Cov.:

AF XY:

0.0217

AC XY:

1617

AN XY:

74396

show subpopulations

Gnomad4 AFR

AF:

0.0168

Gnomad4 AMR

AF:

0.0265

Gnomad4 ASJ

AF:

0.0343

Gnomad4 EAS

AF:

0.00156

Gnomad4 SAS

AF:

0.00809

Gnomad4 FIN

AF:

0.00585

Gnomad4 NFE

AF:

0.0310

Gnomad4 OTH

AF:

0.0185

Alfa

AF:

0.0242

Hom.:

Bravo

AF:

0.0230

Asia WGS

AF:

0.0110

AC:

AN:

3478

EpiCase

AF:

0.0310

EpiControl

AF:

0.0299

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.40

CADD

Benign

1.4

DANN

Benign

0.85

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over