9-94606815-TGG-TG
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_000507.4(FBP1):c.704delC(p.Pro235GlnfsTer42) variant causes a frameshift, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000236 in 1,613,372 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely pathogenic (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_000507.4 frameshift, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
FBP1 | NM_000507.4 | c.704delC | p.Pro235GlnfsTer42 | frameshift_variant, splice_region_variant | Exon 5 of 7 | ENST00000375326.9 | NP_000498.2 | |
FBP1 | NM_001127628.2 | c.704delC | p.Pro235GlnfsTer42 | frameshift_variant, splice_region_variant | Exon 6 of 8 | NP_001121100.1 | ||
FBP1 | XM_006717005.5 | c.458delC | p.Pro153GlnfsTer42 | frameshift_variant, splice_region_variant | Exon 5 of 7 | XP_006717068.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152192Hom.: 0 Cov.: 34
GnomAD4 exome AF: 0.0000253 AC: 37AN: 1461180Hom.: 0 Cov.: 42 AF XY: 0.0000303 AC XY: 22AN XY: 726896
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152192Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0AN XY: 74346
ClinVar
Submissions by phenotype
Fructose-biphosphatase deficiency Pathogenic:4
Likely pathogenic, criteria provided, single submitter | clinical testing | Center for Molecular Medicine, Children’s Hospital of Fudan University | Dec 21, 2022 | - - |
Pathogenic, criteria provided, single submitter | clinical testing;in vitro | Department of Medical Genetics, International Peace Maternity and Child Health Hospital, Shanghai Jiao Tong University School of Medicine | Mar 27, 2017 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Aug 23, 2023 | For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this premature translational stop signal affects FBP1 function (PMID: 28420223). This sequence change creates a premature translational stop signal (p.Pro235Glnfs*42) in the FBP1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 104 amino acid(s) of the FBP1 protein. This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with fructose-1,6-bisphosphatase deficiency (PMID: 28420223, 29203193). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 403705). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. - |
Pathogenic, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | May 18, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at