rs6558541
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1
The ENST00000636934.1(CLN8):c.645A>G(p.Pro215=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.731 in 398,308 control chromosomes in the GnomAD database, including 107,123 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.74 ( 41419 hom., cov: 31)
Exomes 𝑓: 0.73 ( 65704 hom. )
Consequence
CLN8
ENST00000636934.1 synonymous
ENST00000636934.1 synonymous
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -0.161
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 Benign. Variant got -13 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.9).
BP7
?
Synonymous conserved (PhyloP=-0.161 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.782 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CLN8 | ENST00000636934.1 | c.645A>G | p.Pro215= | synonymous_variant | 3/3 | 5 | |||
CLN8 | ENST00000636605.1 | n.133A>G | non_coding_transcript_exon_variant | 2/2 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.736 AC: 111718AN: 151870Hom.: 41398 Cov.: 31
GnomAD3 genomes
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GnomAD4 exome AF: 0.728 AC: 179300AN: 246320Hom.: 65704 Cov.: 0 AF XY: 0.729 AC XY: 91033AN XY: 124812
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GnomAD4 genome ? AF: 0.735 AC: 111781AN: 151988Hom.: 41419 Cov.: 31 AF XY: 0.728 AC XY: 54076AN XY: 74294
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3478
ClinVar
Not reported inComputational scores
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Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at