Genetic Variant JPH3:c.382+778_382+801delCTGCTGCTGCTGCTGCTGCTGCTG (chr16-87604287-CCTGCTGCTGCTGCTGCTGCTGCTG-C) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP3BS2

The NM_001271604.4(JPH3):c.449_472delCTGCTGCTGCTGCTGCTGCTGCTG(p.Ala150_Ala157del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000188 in 1,432,906 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 0.000040 ( 0 hom., cov: 0)

Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

JPH3
NM_001271604.4 disruptive_inframe_deletion

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 -5 ACMG points.

BP3

Nonframeshift variant in repetitive region in NM_001271604.4

BS2

High AC in GnomAd4 at 6 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001271604.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
JPH3	NM_020655.4	MANE Select	c.382+778_382+801delCTGCTGCTGCTGCTGCTGCTGCTG		intron	N/A	NP_065706.2
JPH3	NM_001271604.4		c.449_472delCTGCTGCTGCTGCTGCTGCTGCTG	p.Ala150_Ala157del	disruptive_inframe_deletion	Exon 2 of 2	NP_001258533.1
JPH3	NM_001271605.3		c.147_170delCTGCTGCTGCTGCTGCTGCTGCTG		3_prime_UTR	Exon 2 of 2	NP_001258534.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
JPH3	ENST00000284262.3	TSL:1 MANE Select	c.382+778_382+801delCTGCTGCTGCTGCTGCTGCTGCTG	intron	N/A	ENSP00000284262.2
JPH3	ENST00000301008.5	TSL:1	n.709_732delCTGCTGCTGCTGCTGCTGCTGCTG	non_coding_transcript_exon	Exon 2 of 2
JPH3	ENST00000537256.5	TSL:2	n.96+2376_96+2399delCTGCTGCTGCTGCTGCTGCTGCTG	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0000400

AC:

AN:

149958

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000247

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000593

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000164

AC:

AN:

1282840

Hom.:

AF XY:

0.0000190

AC XY:

AN XY:

633000

show subpopulations

African (AFR)

AF:

0.0000353

AC:

AN:

28328

American (AMR)

AF:

0.0000617

AC:

AN:

32396

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21658

East Asian (EAS)

AF:

0.0000415

AC:

AN:

24078

South Asian (SAS)

AF:

0.0000514

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:

0.0000118

AC:

AN:

1013030

Other (OTH)

AF:

0.0000196

AC:

AN:

51072

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.423

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.0000400

AC:

AN:

150066

Hom.:

Cov.:

AF XY:

0.0000273

AC XY:

AN XY:

73222

show subpopulations

African (AFR)

AF:

0.0000246

AC:

AN:

40668

American (AMR)

AF:

0.00

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:

0.000212

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:

0.0000593

AC:

AN:

67458

Other (OTH)

AF:

0.00

AC:

AN:

2076

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

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 v4.9

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-CCTGCTG

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over