8-1771009-C-T
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Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate
The NM_018941.4(CLN8):c.-46C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000071 in 1,592,354 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 0.000072 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000071 ( 1 hom. )
Consequence
CLN8
NM_018941.4 5_prime_UTR
NM_018941.4 5_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.0680
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 Likely_benign. Variant got -4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.76).
BP6
Variant 8-1771009-C-T is Benign according to our data. Variant chr8-1771009-C-T is described in ClinVar as [Benign]. Clinvar id is 205188.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CLN8 | NM_018941.4 | c.-46C>T | 5_prime_UTR_variant | 2/3 | ENST00000331222.6 | NP_061764.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CLN8 | ENST00000331222.6 | c.-46C>T | 5_prime_UTR_variant | 2/3 | 1 | NM_018941.4 | ENSP00000328182 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000723 AC: 11AN: 152090Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000601 AC: 15AN: 249596Hom.: 0 AF XY: 0.0000740 AC XY: 10AN XY: 135208
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GnomAD4 exome AF: 0.0000708 AC: 102AN: 1440146Hom.: 1 Cov.: 28 AF XY: 0.0000710 AC XY: 51AN XY: 717932
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GnomAD4 genome AF: 0.0000723 AC: 11AN: 152208Hom.: 0 Cov.: 32 AF XY: 0.000108 AC XY: 8AN XY: 74404
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 06, 2015 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Computational scores
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BayesDel_noAF
Benign
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Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at