rs745669920
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The ENST00000256190.13(SBF2):c.257A>T(p.Tyr86Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000116 in 1,461,694 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign 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. Y86C) has been classified as Uncertain significance.
Frequency
Consequence
ENST00000256190.13 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SBF2 | NM_030962.4 | c.257A>T | p.Tyr86Phe | missense_variant | 3/40 | ENST00000256190.13 | NP_112224.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SBF2 | ENST00000256190.13 | c.257A>T | p.Tyr86Phe | missense_variant | 3/40 | 1 | NM_030962.4 | ENSP00000256190 | P3 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251108Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135678
GnomAD4 exome AF: 0.0000116 AC: 17AN: 1461694Hom.: 0 Cov.: 31 AF XY: 0.0000138 AC XY: 10AN XY: 727162
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | May 14, 2020 | The p.Y86F variant (also known as c.257A>T), located in coding exon 3 of the SBF2 gene, results from an A to T substitution at nucleotide position 257. The tyrosine at codon 86 is replaced by phenylalanine, 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 tolerated 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 | Labcorp Genetics (formerly Invitae), Labcorp | Jul 19, 2023 | 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt SBF2 protein function. ClinVar contains an entry for this variant (Variation ID: 476918). This variant has not been reported in the literature in individuals affected with SBF2-related conditions. This variant is present in population databases (rs745669920, gnomAD 0.002%). This sequence change replaces tyrosine, which is neutral and polar, with phenylalanine, which is neutral and non-polar, at codon 86 of the SBF2 protein (p.Tyr86Phe). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at