rs761829741
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_030962.4(SBF2):āc.1061A>Cā(p.Glu354Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000023 in 1,605,490 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 (ā ā ). Synonymous variant affecting the same amino acid position (i.e. E354E) has been classified as Likely benign.
Frequency
Consequence
NM_030962.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SBF2 | NM_030962.4 | c.1061A>C | p.Glu354Ala | missense_variant | 11/40 | ENST00000256190.13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SBF2 | ENST00000256190.13 | c.1061A>C | p.Glu354Ala | missense_variant | 11/40 | 1 | NM_030962.4 | P3 | |
ENST00000667219.1 | n.252-5590T>G | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152218Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000564 AC: 14AN: 248202Hom.: 0 AF XY: 0.0000446 AC XY: 6AN XY: 134582
GnomAD4 exome AF: 0.0000248 AC: 36AN: 1453272Hom.: 0 Cov.: 28 AF XY: 0.0000235 AC XY: 17AN XY: 723536
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152218Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74374
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 28, 2023 | The c.1061A>C (p.E354A) alteration is located in exon 11 (coding exon 11) of the SBF2 gene. This alteration results from a A to C substitution at nucleotide position 1061, causing the glutamic acid (E) at amino acid position 354 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, 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 | Oct 04, 2022 | 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 expected to disrupt SBF2 protein function. ClinVar contains an entry for this variant (Variation ID: 403858). This variant has not been reported in the literature in individuals affected with SBF2-related conditions. This variant is present in population databases (rs761829741, gnomAD 0.06%). This sequence change replaces glutamic acid, which is acidic and polar, with alanine, which is neutral and non-polar, at codon 354 of the SBF2 protein (p.Glu354Ala). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at