rs1288312315
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_030962.4(SBF2):c.5245A>G(p.Thr1749Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,500 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 (★). Synonymous variant affecting the same amino acid position (i.e. T1749T) has been classified as Likely benign.
Frequency
Consequence
NM_030962.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
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.5245A>G | p.Thr1749Ala | missense_variant | 38/40 | ENST00000256190.13 | |
SBF2-AS1 | NR_036485.1 | n.212-23423T>C | intron_variant, non_coding_transcript_variant | ||||
LOC105369149 | XR_007062587.1 | n.171-167T>C | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SBF2 | ENST00000256190.13 | c.5245A>G | p.Thr1749Ala | missense_variant | 38/40 | 1 | NM_030962.4 | P3 | |
SBF2-AS1 | ENST00000663578.1 | n.237-23423T>C | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251368Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135864
GnomAD4 exome AF: 0.00000342 AC: 5AN: 1461500Hom.: 0 Cov.: 30 AF XY: 0.00000413 AC XY: 3AN XY: 727056
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
Charcot-Marie-Tooth disease type 4 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 13, 2019 | This variant is not present in population databases (ExAC no frequency). This sequence change replaces threonine with alanine at codon 1749 of the SBF2 protein (p.Thr1749Ala). The threonine residue is moderately conserved and there is a small physicochemical difference between threonine and alanine. This variant has not been reported in the literature in individuals with SBF2-related disease. 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. 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, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at