8-74244538-TTC-CTT

Variant names:

• chr8-74244538-TTC-CTT
• NM_020647.4:c.1894_1896delGAAinsAAG
• JPH1 p.Glu632Lys

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_020647.4(JPH1):​c.1894_1896delGAAinsAAG​(p.Glu632Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E632Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: JPH1 NM_020647.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.73
• Publications: 0 publications found

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]

JPH1 Gene-Disease associations (from GenCC):

• congenital myopathy 25

  Inheritance: AR Classification: MODERATE Submitted by: G2P

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020647.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	JPH1	NM_020647.4	MANE Select	c.1894_1896delGAAinsAAG	p.Glu632Lys	missense	N/A	NP_065698.1	Q9HDC5
	JPH1	NM_001317830.2		c.1894_1896delGAAinsAAG	p.Glu632Lys	missense	N/A	NP_001304759.1	Q9HDC5
	JPH1	NM_001363050.1		c.1894_1896delGAAinsAAG	p.Glu632Lys	missense	N/A	NP_001349979.1	Q9HDC5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	JPH1	ENST00000342232.5	TSL:1 MANE Select	c.1894_1896delGAAinsAAG	p.Glu632Lys	missense	N/A	ENSP00000344488.4	Q9HDC5
	JPH1	ENST00000519947.1	TSL:1	n.*1289_*1291delGAAinsAAG		non_coding_transcript_exon	Exon 4 of 5	ENSP00000429652.1	E5RHU9
	JPH1	ENST00000519947.1	TSL:1	n.*1289_*1291delGAAinsAAG		3_prime_UTR	Exon 4 of 5	ENSP00000429652.1	E5RHU9

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		5.7

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr8-75156773;