16-87603457-G-A

Position:

• chr16-87603457-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_020655.4(JPH3):​c.311G>A​(p.Gly104Glu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: JPH3 NM_020655.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.03

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.28674746).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
JPH3	NM_020655.4	c.311G>A	p.Gly104Glu	missense_variant	1/5	ENST00000284262.3	NP_065706.2
JPH3	NM_001271604.4	c.311G>A	p.Gly104Glu	missense_variant	1/2		NP_001258533.1
JPH3	NM_001271605.3	c.311G>A	p.Gly104Glu	missense_variant	1/2		NP_001258534.1
JPH3	NR_073379.3	n.96+1527G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
JPH3	ENST00000284262.3	c.311G>A	p.Gly104Glu	missense_variant	1/5	1	NM_020655.4	ENSP00000284262.2
JPH3	ENST00000301008.5	n.571G>A		non_coding_transcript_exon_variant	1/2	1
JPH3	ENST00000537256.5	n.96+1527G>A		intron_variant		2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1410792 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 697160

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center

Oct 12, 2022

Gene of Uncertain Significance -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.39
BayesDel_addAF	Benign	-0.055	T
BayesDel_noAF	Benign	-0.32
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Pathogenic	0.82	D
Eigen	Benign	0.034
Eigen_PC	Benign	0.091
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.29	T
MetaSVM	Benign	-0.66	T
MutationAssessor	Pathogenic	2.9	M
PrimateAI	Pathogenic	0.83	D
PROVEAN	Uncertain	-2.9	D
REVEL	Benign	0.25
Sift	Benign	0.27	T
Sift4G	Benign	0.061	T
Polyphen		0.0020	B
Vest4		0.42
MutPred		0.48		Gain of solvent accessibility (P = 0.0068);
MVP		0.59
MPC		1.6
ClinPred		0.99	D
GERP RS		3.2
Varity_R		0.44
gMVP		0.75

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-87637063;