rs386834123
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1PM4_SupportingPP5
The NM_018941.4(CLN8):c.181_183del(p.Lys61del) variant causes a inframe deletion change involving the alteration of a conserved nucleotide. Variant has been reported in ClinVar as Likely pathogenic (no stars). Synonymous variant affecting the same amino acid position (i.e. E60E) has been classified as Likely benign.
Frequency
Genomes: not found (cov: 32)
Consequence
CLN8
NM_018941.4 inframe_deletion
NM_018941.4 inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 8.40
Genes affected
CLN8 (HGNC:2079): (CLN8 transmembrane ER and ERGIC protein) This gene encodes a transmembrane protein belonging to a family of proteins containing TLC domains, which are postulated to function in lipid synthesis, transport, or sensing. The protein localizes to the endoplasmic reticulum (ER), and may recycle between the ER and ER-Golgi intermediate compartment. Mutations in this gene are associated with a disorder characterized by progressive epilepsy with cognitive disabilities (EPMR), which is a subtype of neuronal ceroid lipofuscinoses (NCL). Patients with mutations in this gene have altered levels of sphingolipid and phospholipids in the brain. [provided by RefSeq, Jul 2017]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM1
?
In a chain Protein CLN8 (size 285) in uniprot entity CLN8_HUMAN there are 49 pathogenic changes around while only 20 benign (71%) in NM_018941.4
PM4
?
Nonframeshift variant in NON repetitive region in NM_018941.4. Strenght limited to Supporting due to length of the change: 1aa.
PP5
?
Variant 8-1771232-GAGA-G is Pathogenic according to our data. Variant chr8-1771232-GAGA-G is described in ClinVar as [Likely_pathogenic]. Clinvar id is 56703.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr8-1771232-GAGA-G is described in Lovd as [Likely_pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CLN8 | NM_018941.4 | c.181_183del | p.Lys61del | inframe_deletion | 2/3 | ENST00000331222.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CLN8 | ENST00000331222.6 | c.181_183del | p.Lys61del | inframe_deletion | 2/3 | 1 | NM_018941.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Pathogenic/Likely pathogenic
Submissions summary: Pathogenic:2
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Neuronal ceroid lipofuscinosis 8 Pathogenic:2
Pathogenic, no assertion criteria provided | literature only | OMIM | Jul 01, 2009 | - - |
Likely pathogenic, no assertion criteria provided | literature only | Juha Muilu Group; Institute for Molecular Medicine Finland (FIMM) | - | - - |
Computational scores
Source:
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Calibrated prediction
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Prediction
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at