Genetic Variant ENST00000301008.5:n.718_732delCTGCTGCTGCTGCTG (chr16-87604287-CCTGCTGCTGCTGCTG-C) – 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.718_732delCTGCTGCTGCTGCTG 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 0.000498 in 1,432,898 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 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 0.00063 ( 0 hom., cov: 0)

Exomes 𝑓: 0.00048 ( 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:

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ACMG classification

Classification was made for transcript

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

BS2

High AC in GnomAd4 at 95 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
JPH3	NM_020655.4 link	c.382+787_382+801delCTGCTGCTGCTGCTG		intron_variant	Intron 1 of 4	ENST00000284262.3	NP_065706.2	Q8WXH2-1B4DIC1F8W9A3
JPH3	NM_001271604.4 link	c.458_472delCTGCTGCTGCTGCTG	p.Ala153_Ala157del	disruptive_inframe_deletion	Exon 2 of 2		NP_001258533.1	F8W9A3Q96HD8
JPH3	NM_001271605.3 link	c.156_170delCTGCTGCTGCTGCTG		3_prime_UTR_variant	Exon 2 of 2		NP_001258534.1	F8W9A3Q96HD8
JPH3	NR_073379.3 link	n.96+2385_96+2399delCTGCTGCTGCTGCTG		intron_variant	Intron 1 of 5

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
JPH3	ENST00000301008.5 link	n.718_732delCTGCTGCTGCTGCTG	non_coding_transcript_exon_variant	Exon 2 of 2	1
JPH3	ENST00000284262.3 link	c.382+787_382+801delCTGCTGCTGCTGCTG	intron_variant	Intron 1 of 4	1	NM_020655.4	ENSP00000284262.2	Q8WXH2-1
JPH3	ENST00000537256.5 link	n.96+2385_96+2399delCTGCTGCTGCTGCTG	intron_variant	Intron 1 of 5	2

Frequencies

GnomAD3 genomes

AF:

0.000627

AC:

AN:

149958

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000542

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000661

Gnomad ASJ

AF:

0.00493

Gnomad EAS

AF:

0.000591

Gnomad SAS

AF:

0.000424

Gnomad FIN

AF:

0.000291

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000548

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000482

AC:

618

AN:

1282832

Hom.:

AF XY:

0.000487

AC XY:

308

AN XY:

632994

show subpopulations

African (AFR)

AF:

0.000424

AC:

AN:

28328

American (AMR)

AF:

0.000401

AC:

AN:

32396

Ashkenazi Jewish (ASJ)

AF:

0.00249

AC:

AN:

21656

East Asian (EAS)

AF:

0.000125

AC:

AN:

24078

South Asian (SAS)

AF:

0.000373

AC:

AN:

77826

European-Finnish (FIN)

AF:

0.0000681

AC:

AN:

29388

Middle Eastern (MID)

AF:

0.00138

AC:

AN:

5062

European-Non Finnish (NFE)

AF:

0.000454

AC:

460

AN:

1013026

Other (OTH)

AF:

0.000744

AC:

AN:

51072

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<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:

0.000633

AC:

AN:

150066

Hom.:

Cov.:

AF XY:

0.000587

AC XY:

AN XY:

73222

show subpopulations

African (AFR)

AF:

0.000566

AC:

AN:

40668

American (AMR)

AF:

0.000660

AC:

AN:

15150

Ashkenazi Jewish (ASJ)

AF:

0.00493

AC:

AN:

3448

East Asian (EAS)

AF:

0.000593

AC:

AN:

5062

South Asian (SAS)

AF:

0.000425

AC:

AN:

4710

European-Finnish (FIN)

AF:

0.000291

AC:

AN:

10302

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.000548

AC:

AN:

67458

Other (OTH)

AF:

0.00

AC:

AN:

2076

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

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

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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