Variant rs9934222 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_020655.4(JPH3):c.768G>A(p.Thr256=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.138 in 1,611,644 control chromosomes in the GnomAD database, including 16,476 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.14 ( 1624 hom., cov: 33)

Exomes 𝑓: 0.14 ( 14852 hom. )

Consequence

JPH3
NM_020655.4 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0730

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.53).

BP6

Variant 16-87644643-G-A is Benign according to our data. Variant chr16-87644643-G-A is described in ClinVar as [Benign]. Clinvar id is 3059867.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.073 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.164 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
JPH3	NM_020655.4 linkuse as main transcript	c.768G>A	p.Thr256=	synonymous_variant	2/5	ENST00000284262.3
JPH3	NR_073379.3 linkuse as main transcript	n.482G>A		non_coding_transcript_exon_variant	2/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
JPH3	ENST00000284262.3 linkuse as main transcript	c.768G>A	p.Thr256=	synonymous_variant	2/5	1	NM_020655.4	P1	Q8WXH2-1
JPH3	ENST00000537256.5 linkuse as main transcript	n.482G>A		non_coding_transcript_exon_variant	2/6	2

Frequencies

GnomAD3 genomes

AF:

0.139

AC:

21173

AN:

151976

Hom.:

1625

Cov.:

show subpopulations

Gnomad AFR

AF:

0.167

Gnomad AMI

AF:

0.200

Gnomad AMR

AF:

0.104

Gnomad ASJ

AF:

0.0988

Gnomad EAS

AF:

0.000972

Gnomad SAS

AF:

0.0735

Gnomad FIN

AF:

0.0910

Gnomad MID

AF:

0.188

Gnomad NFE

AF:

0.154

Gnomad OTH

AF:

0.136

GnomAD3 exomes

AF:

0.113

AC:

28145

AN:

248042

Hom.:

1930

AF XY:

0.113

AC XY:

15208

AN XY:

134432

show subpopulations

Gnomad AFR exome

AF:

0.173

Gnomad AMR exome

AF:

0.0770

Gnomad ASJ exome

AF:

0.106

Gnomad EAS exome

AF:

0.00110

Gnomad SAS exome

AF:

0.0725

Gnomad FIN exome

AF:

0.0861

Gnomad NFE exome

AF:

0.150

Gnomad OTH exome

AF:

0.142

GnomAD4 exome

AF:

0.138

AC:

201731

AN:

1459550

Hom.:

14852

Cov.:

AF XY:

0.137

AC XY:

99371

AN XY:

726148

show subpopulations

Gnomad4 AFR exome

AF:

0.170

Gnomad4 AMR exome

AF:

0.0796

Gnomad4 ASJ exome

AF:

0.106

Gnomad4 EAS exome

AF:

0.000680

Gnomad4 SAS exome

AF:

0.0758

Gnomad4 FIN exome

AF:

0.0854

Gnomad4 NFE exome

AF:

0.153

Gnomad4 OTH exome

AF:

0.131

GnomAD4 genome

AF:

0.139

AC:

21181

AN:

152094

Hom.:

1624

Cov.:

AF XY:

0.133

AC XY:

9874

AN XY:

74338

show subpopulations

Gnomad4 AFR

AF:

0.167

Gnomad4 AMR

AF:

0.104

Gnomad4 ASJ

AF:

0.0988

Gnomad4 EAS

AF:

0.000974

Gnomad4 SAS

AF:

0.0736

Gnomad4 FIN

AF:

0.0910

Gnomad4 NFE

AF:

0.154

Gnomad4 OTH

AF:

0.135

Alfa

AF:

0.143

Hom.:

580

Bravo

AF:

0.140

Asia WGS

AF:

0.0460

AC:

162

AN:

3478

EpiCase

AF:

0.155

EpiControl

AF:

0.155

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

JPH3-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 30, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

6.4

DANN

Benign

0.87

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over