8-74244695-AG-A

Position:

• chr8-74244695-AG-A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP5_Moderate

The NM_020647.4(JPH1):​c.1738delC​(p.Leu580fs) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 31)
• Consequence: JPH1 NM_020647.4 frameshift
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:2
• Conservation: PhyloP100: 2.86

Genes affected

JPH1 (HGNC:14201): (junctophilin 1) 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. This gene is a member of the junctophilin gene family. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 8-74244695-AG-A is Pathogenic according to our data. Variant chr8-74244695-AG-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 2683804.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
JPH1	NM_020647.4	c.1738delC	p.Leu580fs	frameshift_variant	4/6	ENST00000342232.5	NP_065698.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
JPH1	ENST00000342232.5	c.1738delC	p.Leu580fs	frameshift_variant	4/6	1	NM_020647.4	ENSP00000344488.4
JPH1	ENST00000519947.1	n.*1133delC		non_coding_transcript_exon_variant	4/5	1		ENSP00000429652.1
JPH1	ENST00000519947.1	n.*1133delC		3_prime_UTR_variant	4/5	1		ENSP00000429652.1
JPH1	ENST00000518195.1	n.93delC		non_coding_transcript_exon_variant	1/3	4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:2

Revision: criteria provided, single submitter

Submissions by phenotype

CONGENITAL MYOPATHY 25 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Sep 26, 2024

- -

Congenital myopathy Pathogenic:1

Likely pathogenic, criteria provided, single submitter

research

Harry Perkins Institute Of Medical Research, University Of Western Australia

Nov 17, 2023

- -

Computational scores

Source: dbNSFP v4.3

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: chr8-75156930;