rs1555087619
Variant summary
Our verdict is Pathogenic. Variant got 16 ACMG points: 16P and 0B. PVS1_ModeratePM2PP3_StrongPP5_Very_Strong
The NM_030813.6(CLPB):c.1156+1G>A variant causes a splice donor change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,630 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Likely pathogenic (★★).
Frequency
Consequence
NM_030813.6 splice_donor
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 16 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CLPB | NM_001258392.3 | c.1066+1G>A | splice_donor_variant | ENST00000538039.6 | |||
CLPB | NM_030813.6 | c.1156+1G>A | splice_donor_variant | ENST00000294053.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CLPB | ENST00000294053.9 | c.1156+1G>A | splice_donor_variant | 1 | NM_030813.6 | P4 | |||
CLPB | ENST00000538039.6 | c.1066+1G>A | splice_donor_variant | 2 | NM_001258392.3 | A1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461630Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 727132
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Inborn genetic diseases Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 31, 2016 | - - |
3-methylglutaconic aciduria, type VIIB Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jan 24, 2023 | In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 520785). This variant has not been reported in the literature in individuals affected with CLPB-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change affects a donor splice site in intron 9 of the CLPB gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in CLPB are known to be pathogenic (PMID: 25597510, 28687938). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at