rs1404020990
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3PP5
The NM_002972.4(SBF1):c.4378T>G(p.Leu1460Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000548 in 1,460,094 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_002972.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SBF1 | NM_002972.4 | c.4378T>G | p.Leu1460Val | missense_variant | 33/41 | ENST00000380817.8 | |
SBF1 | NM_001410794.1 | c.4381T>G | p.Leu1461Val | missense_variant | 33/41 | ||
SBF1 | NM_001365819.1 | c.4303T>G | p.Leu1435Val | missense_variant | 32/40 | ||
SBF1 | NM_001410795.1 | c.4300T>G | p.Leu1434Val | missense_variant | 32/40 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SBF1 | ENST00000380817.8 | c.4378T>G | p.Leu1460Val | missense_variant | 33/41 | 1 | NM_002972.4 | P3 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 exomes AF: 0.00000807 AC: 2AN: 247760Hom.: 0 AF XY: 0.00000742 AC XY: 1AN XY: 134694
GnomAD4 exome AF: 0.00000548 AC: 8AN: 1460094Hom.: 0 Cov.: 33 AF XY: 0.00000688 AC XY: 5AN XY: 726254
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
Charcot-Marie-Tooth disease type 4B3 Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Genomic Research Center, Shahid Beheshti University of Medical Sciences | May 03, 2020 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Feb 18, 2022 | Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 522645). This variant has not been reported in the literature in individuals affected with SBF1-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.002%). This sequence change replaces leucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1460 of the SBF1 protein (p.Leu1460Val). 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at