Variant 16-87604287-CCTGCTGCTGCTGCTGCTGCTGCTGCTG-CCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTG details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP3BS1BS2

The NM_001271604.4(JPH3):c.458_472dupCTGCTGCTGCTGCTG(p.Ala153_Ala157dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.012 ( 39 hom., cov: 0)

Exomes 𝑓: 0.0020 ( 61 hom. )

Failed GnomAD Quality Control

Consequence

JPH3
NM_001271604.4 disruptive_inframe_insertion

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.966

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 -9 ACMG points.

BP3

Nonframeshift variant in repetitive region in NM_001271604.4

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0124 (1861/150056) while in subpopulation AFR AF= 0.0412 (1674/40658). AF 95% confidence interval is 0.0395. There are 39 homozygotes in gnomad4. There are 841 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1861 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
JPH3	NM_020655.4 linkuse as main transcript	c.382+787_382+801dupCTGCTGCTGCTGCTG		intron_variant		ENST00000284262.3	NP_065706.2	Q8WXH2-1B4DIC1F8W9A3
JPH3	NM_001271604.4 linkuse as main transcript	c.458_472dupCTGCTGCTGCTGCTG	p.Ala153_Ala157dup	disruptive_inframe_insertion	2/2		NP_001258533.1	F8W9A3Q96HD8
JPH3	NM_001271605.3 linkuse as main transcript	c.156_170dupCTGCTGCTGCTGCTG		3_prime_UTR_variant	2/2		NP_001258534.1	F8W9A3Q96HD8
JPH3	NR_073379.3 linkuse as main transcript	n.96+2385_96+2399dupCTGCTGCTGCTGCTG		intron_variant

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	UniProt
JPH3	ENST00000284262.3 linkuse as main transcript	c.382+787_382+801dupCTGCTGCTGCTGCTG	intron_variant		1	NM_020655.4	ENSP00000284262.2	Q8WXH2-1
JPH3	ENST00000301008.5 linkuse as main transcript	n.718_732dupCTGCTGCTGCTGCTG	non_coding_transcript_exon_variant	2/2	1
JPH3	ENST00000537256.5 linkuse as main transcript	n.96+2385_96+2399dupCTGCTGCTGCTGCTG	intron_variant		2

Frequencies

GnomAD3 genomes

AF:

0.0124

AC:

1857

AN:

149948

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0412

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00568

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000197

Gnomad SAS

AF:

0.00170

Gnomad FIN

AF:

0.000194

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.000934

Gnomad OTH

AF:

0.0107

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00195

AC:

2504

AN:

1282726

Hom.:

Cov.:

AF XY:

0.00180

AC XY:

1138

AN XY:

632932

show subpopulations

Gnomad4 AFR exome

AF:

0.0447

Gnomad4 AMR exome

AF:

0.00432

Gnomad4 ASJ exome

AF:

0.0000923

Gnomad4 EAS exome

AF:

0.00183

Gnomad4 SAS exome

AF:

0.00125

Gnomad4 FIN exome

AF:

0.000272

Gnomad4 NFE exome

AF:

0.000727

Gnomad4 OTH exome

AF:

0.00362

GnomAD4 genome

AF:

0.0124

AC:

1861

AN:

150056

Hom.:

Cov.:

AF XY:

0.0115

AC XY:

841

AN XY:

73218

show subpopulations

Gnomad4 AFR

AF:

0.0412

Gnomad4 AMR

AF:

0.00568

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000198

Gnomad4 SAS

AF:

0.00170

Gnomad4 FIN

AF:

0.000194

Gnomad4 NFE

AF:

0.000934

Gnomad4 OTH

AF:

0.0111

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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