Genetic Variant JPH3:n.706_732dupCTGCTGCTGCTGCTGCTGCTGCTGCTG (chr16-87604287-C-CCTGCTGCTGCTGCTGCTGCTGCTGCTG) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The ENST00000301008.5(JPH3):n.706_732dupCTGCTGCTGCTGCTGCTGCTGCTGCTG variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00013 in 1,432,886 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00032 ( 0 hom., cov: 0)

Exomes 𝑓: 0.00011 ( 0 hom. )

Consequence

JPH3
ENST00000301008.5 non_coding_transcript_exon

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.966

Publications

1 publications found

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 Gene-Disease associations (from GenCC):

Huntington disease-like 2
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics

JPH3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2

High AC in GnomAd4 at 48 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
JPH3	NM_020655.4 link	c.382+775_382+801dupCTGCTGCTGCTGCTGCTGCTGCTGCTG		intron_variant	Intron 1 of 4	ENST00000284262.3	NP_065706.2	Q8WXH2-1B4DIC1F8W9A3
JPH3	NM_001271604.4 link	c.446_472dupCTGCTGCTGCTGCTGCTGCTGCTGCTG	p.Ala149_Ala157dup	disruptive_inframe_insertion	Exon 2 of 2		NP_001258533.1	F8W9A3Q96HD8
JPH3	NM_001271605.3 link	c.144_170dupCTGCTGCTGCTGCTGCTGCTGCTGCTG		3_prime_UTR_variant	Exon 2 of 2		NP_001258534.1	F8W9A3Q96HD8
JPH3	NR_073379.3 link	n.96+2373_96+2399dupCTGCTGCTGCTGCTGCTGCTGCTGCTG		intron_variant	Intron 1 of 5

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
JPH3	ENST00000301008.5 link	n.706_732dupCTGCTGCTGCTGCTGCTGCTGCTGCTG	non_coding_transcript_exon_variant	Exon 2 of 2	1
JPH3	ENST00000284262.3 link	c.382+775_382+801dupCTGCTGCTGCTGCTGCTGCTGCTGCTG	intron_variant	Intron 1 of 4	1	NM_020655.4	ENSP00000284262.2	Q8WXH2-1
JPH3	ENST00000537256.5 link	n.96+2373_96+2399dupCTGCTGCTGCTGCTGCTGCTGCTGCTG	intron_variant	Intron 1 of 5	2

Frequencies

GnomAD3 genomes

AF:

0.000320

AC:

AN:

149956

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000542

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000198

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000212

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000326

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000108

AC:

138

AN:

1282822

Hom.:

Cov.:

AF XY:

0.000109

AC XY:

AN XY:

632998

show subpopulations

African (AFR)

AF:

0.000318

AC:

AN:

28324

American (AMR)

AF:

0.000340

AC:

AN:

32396

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21658

East Asian (EAS)

AF:

0.000249

AC:

AN:

24076

South Asian (SAS)

AF:

0.0000128

AC:

AN:

77828

European-Finnish (FIN)

AF:

0.000102

AC:

AN:

29388

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5062

European-Non Finnish (NFE)

AF:

0.000102

AC:

103

AN:

1013024

Other (OTH)

AF:

0.0000979

AC:

AN:

51066

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000320

AC:

AN:

150064

Hom.:

Cov.:

AF XY:

0.000382

AC XY:

AN XY:

73220

show subpopulations

African (AFR)

AF:

0.000541

AC:

AN:

40668

American (AMR)

AF:

0.000198

AC:

AN:

15148

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3448

East Asian (EAS)

AF:

0.00

AC:

AN:

5062

South Asian (SAS)

AF:

0.000212

AC:

AN:

4710

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10302

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.000326

AC:

AN:

67458

Other (OTH)

AF:

0.00

AC:

AN:

2076

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

316

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.97

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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16-87604287-CCTGCTGCTGCTGCTGCTGCTGCTGCTGCTG-CCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTG

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over