rs148131421

Positions:

• chr16-87644830-C-A
• chr16-87644830-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Moderate BP6_Moderate BS2

The NM_020655.4(JPH3):​c.955C>A​(p.Arg319=) variant causes a synonymous change. The variant allele was found at a frequency of 0.00128 in 1,613,304 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00075 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0013 (1 hom.)
• Consequence: JPH3 NM_020655.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.89

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]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.22).
• BP6: Variant 16-87644830-C-A is Benign according to our data. Variant chr16-87644830-C-A is described in ClinVar as [Benign]. Clinvar id is 716816.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 114 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
JPH3	NM_020655.4	c.955C>A	p.Arg319=	synonymous_variant	2/5	ENST00000284262.3
JPH3	NR_073379.3	n.669C>A		non_coding_transcript_exon_variant	2/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
JPH3	ENST00000284262.3	c.955C>A	p.Arg319=	synonymous_variant	2/5	1	NM_020655.4	P1
JPH3	ENST00000537256.5	n.669C>A		non_coding_transcript_exon_variant	2/6	2

Frequencies

GnomAD3 genomes AF: 0.000750 AC: 114 AN: 151942 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000314

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00111

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00121

Gnomad OTH AF: 0.000958

GnomAD3 exomes AF: 0.000640 AC: 160 AN: 249924 Hom.: 1 AF XY: 0.000658 AC XY: 89 AN XY: 135316

Gnomad AFR exome AF: 0.000435

Gnomad AMR exome AF: 0.000666

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000469

Gnomad NFE exome AF: 0.00111

Gnomad OTH exome AF: 0.000655

GnomAD4 exome AF: 0.00133 AC: 1945 AN: 1461244 Hom.: 1 Cov.: 37 AF XY: 0.00127 AC XY: 925 AN XY: 726988

Gnomad4 AFR exome AF: 0.000299

Gnomad4 AMR exome AF: 0.000649

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.0000378

Gnomad4 NFE exome AF: 0.00160

Gnomad4 OTH exome AF: 0.00199

GnomAD4 genome AF: 0.000750 AC: 114 AN: 152060 Hom.: 0 Cov.: 32 AF XY: 0.000632 AC XY: 47 AN XY: 74330

Gnomad4 AFR AF: 0.000313

Gnomad4 AMR AF: 0.00111

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00121

Gnomad4 OTH AF: 0.000948

Alfa AF: 0.000708 Hom.: 0

Bravo AF: 0.000854

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00109

EpiControl AF: 0.00130

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jun 08, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.22
CADD	Benign	7.3
DANN	Benign	0.64

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

LitVar

Other links and lift over

dbSNP: rs148131421; hg19: chr16-87678436;