rs745312608
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP6
The NM_006493.4(CLN5):c.565+3_565+4dupAA variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000342 in 1,609,296 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_006493.4 splice_region, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CLN5 | NM_006493.4 | c.565+3_565+4dupAA | splice_region_variant, intron_variant | Intron 3 of 3 | ENST00000377453.9 | NP_006484.2 | ||
CLN5 | NM_001366624.2 | c.565+3_565+4dupAA | splice_region_variant, intron_variant | Intron 3 of 4 | NP_001353553.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CLN5 | ENST00000377453.9 | c.565+3_565+4dupAA | splice_region_variant, intron_variant | Intron 3 of 3 | 1 | NM_006493.4 | ENSP00000366673.5 | |||
ENSG00000283208 | ENST00000638147.2 | c.565+3_565+4dupAA | splice_region_variant, intron_variant | Intron 3 of 4 | 5 | ENSP00000490953.2 |
Frequencies
GnomAD3 genomes AF: 0.000164 AC: 25AN: 152176Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000478 AC: 12AN: 251262Hom.: 0 AF XY: 0.0000294 AC XY: 4AN XY: 135858
GnomAD4 exome AF: 0.0000206 AC: 30AN: 1457002Hom.: 0 Cov.: 28 AF XY: 0.0000193 AC XY: 14AN XY: 725172
GnomAD4 genome AF: 0.000164 AC: 25AN: 152294Hom.: 0 Cov.: 33 AF XY: 0.000161 AC XY: 12AN XY: 74470
ClinVar
Submissions by phenotype
Neuronal ceroid lipofuscinosis Uncertain:2
This sequence change falls in intron 3 of the CLN5 gene. It does not directly change the encoded amino acid sequence of the CLN5 protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs745312608, gnomAD 0.06%). This variant has not been reported in the literature in individuals affected with CLN5-related conditions. ClinVar contains an entry for this variant (Variation ID: 457967). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -
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Inborn genetic diseases Uncertain:1
The c.712+3_712+4dupAA alteration is located in Intron 3 (E) of the CLN5 gene. This alteration consists of a duplication of 2 nucleotides at nucleotide position c.7123 within Intron 3 (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
not provided Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at