Genetic Variant JPH3:n.715_732delCTGCTGCTGCTGCTGCTG (chr16-87604287-CCTGCTGCTGCTGCTGCTG-C) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1BS2

The ENST00000301008.5(JPH3):n.715_732delCTGCTGCTGCTGCTGCTG 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 0.00118 in 1,432,806 control chromosomes in the GnomAD database, including 11 homozygotes. It is difficult to determine the true allele frequency of this variant because it is of type DEL_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 0.0059 ( 7 hom., cov: 0)

Exomes 𝑓: 0.00062 ( 4 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: Benign. The variant received -8 ACMG points.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00594 (892/150066) while in subpopulation AFR AF = 0.0196 (797/40668). AF 95% confidence interval is 0.0185. There are 7 homozygotes in GnomAd4. There are 426 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.

BS2

High AC in GnomAd4 at 892 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
JPH3	NM_020655.4 link	c.382+784_382+801delCTGCTGCTGCTGCTGCTG		intron_variant	Intron 1 of 4	ENST00000284262.3	NP_065706.2	Q8WXH2-1B4DIC1F8W9A3
JPH3	NM_001271604.4 link	c.455_472delCTGCTGCTGCTGCTGCTG	p.Ala152_Ala157del	disruptive_inframe_deletion	Exon 2 of 2		NP_001258533.1	F8W9A3Q96HD8
JPH3	NM_001271605.3 link	c.153_170delCTGCTGCTGCTGCTGCTG		3_prime_UTR_variant	Exon 2 of 2		NP_001258534.1	F8W9A3Q96HD8
JPH3	NR_073379.3 link	n.96+2382_96+2399delCTGCTGCTGCTGCTGCTG		intron_variant	Intron 1 of 5

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
JPH3	ENST00000301008.5 link	n.715_732delCTGCTGCTGCTGCTGCTG	non_coding_transcript_exon_variant	Exon 2 of 2	1
JPH3	ENST00000284262.3 link	c.382+784_382+801delCTGCTGCTGCTGCTGCTG	intron_variant	Intron 1 of 4	1	NM_020655.4	ENSP00000284262.2	Q8WXH2-1
JPH3	ENST00000537256.5 link	n.96+2382_96+2399delCTGCTGCTGCTGCTGCTG	intron_variant	Intron 1 of 5	2

Frequencies

GnomAD3 genomes

AF:

0.00594

AC:

890

AN:

149958

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0196

Gnomad AMI

AF:

0.00111

Gnomad AMR

AF:

0.00403

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000394

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000971

Gnomad MID

AF:

0.00318

Gnomad NFE

AF:

0.000237

Gnomad OTH

AF:

0.00633

GnomAD4 exome

AF:

0.000619

AC:

794

AN:

1282740

Hom.:

AF XY:

0.000558

AC XY:

353

AN XY:

632954

show subpopulations

African (AFR)

AF:

0.0174

AC:

493

AN:

28276

American (AMR)

AF:

0.00142

AC:

AN:

32374

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21656

East Asian (EAS)

AF:

0.000166

AC:

AN:

24078

South Asian (SAS)

AF:

0.000360

AC:

AN:

77822

European-Finnish (FIN)

AF:

0.000170

AC:

AN:

29386

Middle Eastern (MID)

AF:

0.00237

AC:

AN:

5062

European-Non Finnish (NFE)

AF:

0.000137

AC:

139

AN:

1013026

Other (OTH)

AF:

0.00131

AC:

AN:

51060

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

120

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

104

130

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00594

AC:

892

AN:

150066

Hom.:

Cov.:

AF XY:

0.00582

AC XY:

426

AN XY:

73222

show subpopulations

African (AFR)

AF:

0.0196

AC:

797

AN:

40668

American (AMR)

AF:

0.00403

AC:

AN:

15150

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3448

East Asian (EAS)

AF:

0.000395

AC:

AN:

5062

South Asian (SAS)

AF:

0.00

AC:

AN:

4710

European-Finnish (FIN)

AF:

0.0000971

AC:

AN:

10302

Middle Eastern (MID)

AF:

0.00342

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.000237

AC:

AN:

67458

Other (OTH)

AF:

0.00626

AC:

AN:

2076

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

129

172

215

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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