rs200594508
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_030962.4(SBF2):āc.3877A>Gā(p.Lys1293Glu) variant causes a missense change. The variant allele was found at a frequency of 0.0000886 in 1,614,070 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. K1293R) 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 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SBF2 | NM_030962.4 | c.3877A>G | p.Lys1293Glu | missense_variant | 29/40 | ENST00000256190.13 | |
SBF2 | NM_001386339.1 | c.3973A>G | p.Lys1325Glu | missense_variant | 30/41 | ||
SBF2 | NM_001386342.1 | c.3748A>G | p.Lys1250Glu | missense_variant | 28/39 | ||
SBF2 | XM_047427657.1 | c.3973A>G | p.Lys1325Glu | missense_variant | 30/35 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SBF2 | ENST00000256190.13 | c.3877A>G | p.Lys1293Glu | missense_variant | 29/40 | 1 | NM_030962.4 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000723 AC: 11AN: 152184Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000119 AC: 30AN: 251400Hom.: 0 AF XY: 0.000118 AC XY: 16AN XY: 135884
GnomAD4 exome AF: 0.0000903 AC: 132AN: 1461886Hom.: 0 Cov.: 30 AF XY: 0.000105 AC XY: 76AN XY: 727242
GnomAD4 genome ? AF: 0.0000723 AC: 11AN: 152184Hom.: 0 Cov.: 32 AF XY: 0.0000807 AC XY: 6AN XY: 74336
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 06, 2020 | The p.K1293E variant (also known as c.3877A>G), located in coding exon 29 of the SBF2 gene, results from an A to G substitution at nucleotide position 3877. The lysine at codon 1293 is replaced by glutamic acid, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. 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 12, 2022 | This sequence change replaces lysine, which is basic and polar, with glutamic acid, which is acidic and polar, at codon 1293 of the SBF2 protein (p.Lys1293Glu). This variant is present in population databases (rs200594508, gnomAD 0.07%). This variant has not been reported in the literature in individuals affected with SBF2-related conditions. ClinVar contains an entry for this variant (Variation ID: 476927). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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