Genetic Variant JPH3:n.694_732dupCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTG (chr16-87604287-C-CCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTG) – 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.694_732dupCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTG variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. 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 0.0023 ( 3 hom., cov: 0)

Exomes 𝑓: 0.00011 ( 2 hom. )

Failed GnomAD Quality Control

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 351 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
JPH3	NM_020655.4 link	c.382+763_382+801dupCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTG		intron_variant	Intron 1 of 4	ENST00000284262.3	NP_065706.2	Q8WXH2-1B4DIC1F8W9A3
JPH3	NM_001271604.4 link	c.434_472dupCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTG	p.Ala145_Ala157dup	disruptive_inframe_insertion	Exon 2 of 2		NP_001258533.1	F8W9A3Q96HD8
JPH3	NM_001271605.3 link	c.132_170dupCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTG		3_prime_UTR_variant	Exon 2 of 2		NP_001258534.1	F8W9A3Q96HD8
JPH3	NR_073379.3 link	n.96+2361_96+2399dupCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTG		intron_variant	Intron 1 of 5

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
JPH3	ENST00000301008.5 link	n.694_732dupCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTG	non_coding_transcript_exon_variant	Exon 2 of 2	1
JPH3	ENST00000284262.3 link	c.382+763_382+801dupCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTG	intron_variant	Intron 1 of 4	1	NM_020655.4	ENSP00000284262.2	Q8WXH2-1
JPH3	ENST00000537256.5 link	n.96+2361_96+2399dupCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTG	intron_variant	Intron 1 of 5	2

Frequencies

GnomAD3 genomes

AF:

0.00234

AC:

351

AN:

149948

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00836

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000661

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000148

Gnomad OTH

AF:

0.000487

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000108

AC:

139

AN:

1282834

Hom.:

Cov.:

AF XY:

0.0000853

AC XY:

AN XY:

632996

show subpopulations

African (AFR)

AF:

0.00346

AC:

AN:

28318

American (AMR)

AF:

0.000432

AC:

AN:

32398

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21658

East Asian (EAS)

AF:

0.00

AC:

AN:

24078

South Asian (SAS)

AF:

0.0000128

AC:

AN:

77828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

29388

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5062

European-Non Finnish (NFE)

AF:

0.00000691

AC:

AN:

1013034

Other (OTH)

AF:

0.000372

AC:

AN:

51070

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.454

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00234

AC:

351

AN:

150056

Hom.:

Cov.:

AF XY:

0.00223

AC XY:

163

AN XY:

73216

show subpopulations

African (AFR)

AF:

0.00834

AC:

339

AN:

40658

American (AMR)

AF:

0.000660

AC:

AN:

15150

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3448

East Asian (EAS)

AF:

0.00

AC:

AN:

5062

South Asian (SAS)

AF:

0.00

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:

0.0000148

AC:

AN:

67458

Other (OTH)

AF:

0.000482

AC:

AN:

2076

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.457

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

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-CCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTG

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