rs746685729
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_030962.4(SBF2):āc.1045A>Gā(p.Lys349Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000102 in 1,181,160 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 ).
Frequency
Genomes: not found (cov: 32)
Exomes š: 0.000010 ( 0 hom. )
Consequence
SBF2
NM_030962.4 missense
NM_030962.4 missense
Scores
4
7
8
Clinical Significance
Conservation
PhyloP100: 3.35
Genes affected
SBF2 (HGNC:2135): (SET binding factor 2) This gene encodes a pseudophosphatase and member of the myotubularin-related protein family. This gene maps within the CMT4B2 candidate region of chromosome 11p15 and mutations in this gene have been associated with Charcot-Marie-Tooth Disease, type 4B2. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.3457458).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SBF2 | NM_030962.4 | c.1045A>G | p.Lys349Glu | missense_variant | 10/40 | ENST00000256190.13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SBF2 | ENST00000256190.13 | c.1045A>G | p.Lys349Glu | missense_variant | 10/40 | 1 | NM_030962.4 | P3 | |
ENST00000667219.1 | n.252-4757T>C | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251228Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135840
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GnomAD4 exome AF: 0.0000102 AC: 12AN: 1181160Hom.: 0 Cov.: 20 AF XY: 0.0000117 AC XY: 7AN XY: 600676
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GnomAD4 genome ? Cov.: 32
GnomAD4 genome
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32
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Charcot-Marie-Tooth disease Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Molecular Genetics Laboratory, London Health Sciences Centre | - | - - |
Charcot-Marie-Tooth disease type 4 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 27, 2023 | This sequence change replaces lysine, which is basic and polar, with glutamic acid, which is acidic and polar, at codon 349 of the SBF2 protein (p.Lys349Glu). This variant is present in population databases (rs746685729, gnomAD 0.0009%). 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: 403855). 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. 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:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D
M_CAP
Benign
D
MetaRNN
Benign
T
MetaSVM
Uncertain
T
MutationAssessor
Benign
L
MutationTaster
Benign
D
PrimateAI
Pathogenic
D
PROVEAN
Benign
N
REVEL
Uncertain
Sift
Benign
T
Sift4G
Benign
T
Polyphen
P
Vest4
MutPred
Loss of ubiquitination at K349 (P = 0.0127);
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at