rs747269745
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PVS1_ModeratePM2PP5
The NM_000507.4(FBP1):c.966delC(p.Asp323ThrfsTer7) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,814 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_000507.4 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
FBP1 | NM_000507.4 | c.966delC | p.Asp323ThrfsTer7 | frameshift_variant | Exon 7 of 7 | ENST00000375326.9 | NP_000498.2 | |
FBP1 | NM_001127628.2 | c.966delC | p.Asp323ThrfsTer7 | frameshift_variant | Exon 8 of 8 | NP_001121100.1 | ||
FBP1 | XM_006717005.5 | c.720delC | p.Asp241ThrfsTer7 | frameshift_variant | Exon 7 of 7 | XP_006717068.1 |
Ensembl
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251162Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135758
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1461814Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1AN XY: 727200
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Fructose-biphosphatase deficiency Pathogenic:1Uncertain:1
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This sequence change creates a premature translational stop signal (p.Asp323Thrfs*7) in the FBP1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 16 amino acid(s) of the FBP1 protein. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This premature translational stop signal has been observed in individual(s) with fructose-1,6-bisphosphatase deficiency (PMID: 10234608). ClinVar contains an entry for this variant (Variation ID: 548499). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. Experimental studies have shown that this premature translational stop signal affects FBP1 function (PMID: 10234608). This variant disrupts a region of the FBP1 protein in which other variant(s) (p.Leu329Pro) have been determined to be pathogenic (PMID: 30858132). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at