rs753298285
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_030962.4(SBF2):c.2828G>A(p.Arg943Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000411 in 1,461,528 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 Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R943W) has been classified as Uncertain significance.
Frequency
Consequence
NM_030962.4 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 |
---|---|---|---|---|---|---|---|
SBF2 | NM_030962.4 | c.2828G>A | p.Arg943Gln | missense_variant | 23/40 | ENST00000256190.13 | |
LOC101928008 | NR_120539.1 | n.135+7786C>T | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SBF2 | ENST00000256190.13 | c.2828G>A | p.Arg943Gln | missense_variant | 23/40 | 1 | NM_030962.4 | P3 | |
ENST00000533659.1 | n.134+7786C>T | intron_variant, non_coding_transcript_variant | 1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.0000239 AC: 6AN: 251320Hom.: 0 AF XY: 0.0000294 AC XY: 4AN XY: 135840
GnomAD4 exome AF: 0.0000411 AC: 60AN: 1461528Hom.: 0 Cov.: 31 AF XY: 0.0000385 AC XY: 28AN XY: 727074
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 16, 2019 | The p.R943Q variant (also known as c.2828G>A), located in coding exon 23 of the SBF2 gene, results from a G to A substitution at nucleotide position 2828. The arginine at codon 943 is replaced by glutamine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Charcot-Marie-Tooth disease type 4 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 30, 2021 | This sequence change replaces arginine with glutamine at codon 943 of the SBF2 protein (p.Arg943Gln). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs753298285, ExAC 0.006%). This variant has not been reported in the literature in individuals affected with SBF2-related conditions. 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: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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