dbSNP rs2562059: JPH3:c.382+1721C>G (chr16-87605249-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_020655.4(JPH3):c.382+1721C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.501 in 152,098 control chromosomes in the GnomAD database, including 20,563 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.50 ( 20563 hom., cov: 32)

Consequence

JPH3
NM_020655.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.83

Publications

3 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.684 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
JPH3	NM_020655.4 link	c.382+1721C>G		intron_variant	Intron 1 of 4	ENST00000284262.3	NP_065706.2	Q8WXH2-1B4DIC1F8W9A3
JPH3	NR_073379.3 link	n.96+3319C>G		intron_variant	Intron 1 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
JPH3	ENST00000284262.3 link	c.382+1721C>G		intron_variant	Intron 1 of 4	1	NM_020655.4	ENSP00000284262.2		Q8WXH2-1
JPH3	ENST00000537256.5 link	n.96+3319C>G		intron_variant	Intron 1 of 5	2

Frequencies

GnomAD3 genomes

AF:

0.501

AC:

76107

AN:

151978

Hom.:

20529

Cov.:

show subpopulations

Gnomad AFR

AF:

0.690

Gnomad AMI

AF:

0.390

Gnomad AMR

AF:

0.363

Gnomad ASJ

AF:

0.427

Gnomad EAS

AF:

0.129

Gnomad SAS

AF:

0.390

Gnomad FIN

AF:

0.516

Gnomad MID

AF:

0.500

Gnomad NFE

AF:

0.456

Gnomad OTH

AF:

0.495

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.501

AC:

76189

AN:

152098

Hom.:

20563

Cov.:

AF XY:

0.496

AC XY:

36881

AN XY:

74344

show subpopulations

African (AFR)

AF:

0.691

AC:

28652

AN:

41482

American (AMR)

AF:

0.362

AC:

5532

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.427

AC:

1480

AN:

3468

East Asian (EAS)

AF:

0.129

AC:

669

AN:

5172

South Asian (SAS)

AF:

0.389

AC:

1874

AN:

4814

European-Finnish (FIN)

AF:

0.516

AC:

5463

AN:

10582

Middle Eastern (MID)

AF:

0.503

AC:

148

AN:

294

European-Non Finnish (NFE)

AF:

0.456

AC:

30976

AN:

67974

Other (OTH)

AF:

0.493

AC:

1040

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1814

3628

5441

7255

9069

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

660

1320

1980

2640

3300

<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:

0.489

Hom.:

2348

Bravo

AF:

0.493

Asia WGS

AF:

0.302

AC:

1056

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.089

(source)

DANN

Benign

0.43

PhyloP100

-2.8

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over