chr16-87604287-CCTGCTGCTGCTGCTGCTG-C

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

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
JPH3NM_020655.4 linkc.382+784_382+801delCTGCTGCTGCTGCTGCTG intron_variant Intron 1 of 4 ENST00000284262.3 NP_065706.2 Q8WXH2-1B4DIC1F8W9A3
JPH3NM_001271604.4 linkc.455_472delCTGCTGCTGCTGCTGCTG p.Ala152_Ala157del disruptive_inframe_deletion Exon 2 of 2 NP_001258533.1 F8W9A3Q96HD8
JPH3NM_001271605.3 linkc.*153_*170delCTGCTGCTGCTGCTGCTG 3_prime_UTR_variant Exon 2 of 2 NP_001258534.1 F8W9A3Q96HD8
JPH3NR_073379.3 linkn.96+2382_96+2399delCTGCTGCTGCTGCTGCTG intron_variant Intron 1 of 5

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
JPH3ENST00000301008.5 linkn.715_732delCTGCTGCTGCTGCTGCTG non_coding_transcript_exon_variant Exon 2 of 2 1
JPH3ENST00000284262.3 linkc.382+784_382+801delCTGCTGCTGCTGCTGCTG intron_variant Intron 1 of 4 1 NM_020655.4 ENSP00000284262.2 Q8WXH2-1
JPH3ENST00000537256.5 linkn.96+2382_96+2399delCTGCTGCTGCTGCTGCTG intron_variant Intron 1 of 5 2

Frequencies

GnomAD3 genomes
AF:
0.00594
AC:
890
AN:
149958
Hom.:
7
Cov.:
0
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.:
4
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:
46
AN:
32374
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
21656
East Asian (EAS)
AF:
0.000166
AC:
4
AN:
24078
South Asian (SAS)
AF:
0.000360
AC:
28
AN:
77822
European-Finnish (FIN)
AF:
0.000170
AC:
5
AN:
29386
Middle Eastern (MID)
AF:
0.00237
AC:
12
AN:
5062
European-Non Finnish (NFE)
AF:
0.000137
AC:
139
AN:
1013026
Other (OTH)
AF:
0.00131
AC:
67
AN:
51060
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.484
Heterozygous variant carriers
0
24
48
72
96
120
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
26
52
78
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.:
7
Cov.:
0
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:
61
AN:
15150
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3448
East Asian (EAS)
AF:
0.000395
AC:
2
AN:
5062
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4710
European-Finnish (FIN)
AF:
0.0000971
AC:
1
AN:
10302
Middle Eastern (MID)
AF:
0.00342
AC:
1
AN:
292
European-Non Finnish (NFE)
AF:
0.000237
AC:
16
AN:
67458
Other (OTH)
AF:
0.00626
AC:
13
AN:
2076
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.509
Heterozygous variant carriers
0
43
86
129
172
215
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
10
20
30
40
50
<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

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs71156237; hg19: chr16-87637893; API