chrX-40052377-G-A
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP3BS2
The NM_001123385.2(BCOR):c.5000C>T(p.Ser1667Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000911 in 1,097,199 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 hemizygotes in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. S1667S) has been classified as Likely benign.
Frequency
Consequence
NM_001123385.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BCOR | NM_001123385.2 | c.5000C>T | p.Ser1667Leu | missense_variant | 15/15 | ENST00000378444.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BCOR | ENST00000378444.9 | c.5000C>T | p.Ser1667Leu | missense_variant | 15/15 | 1 | NM_001123385.2 | P2 |
Frequencies
GnomAD3 genomes ? Cov.: 23
GnomAD3 exomes AF: 0.0000491 AC: 9AN: 183204Hom.: 0 AF XY: 0.0000590 AC XY: 4AN XY: 67812
GnomAD4 exome AF: 0.00000911 AC: 10AN: 1097199Hom.: 0 Cov.: 30 AF XY: 0.00000827 AC XY: 3AN XY: 362601
GnomAD4 genome ? Cov.: 23
ClinVar
Submissions by phenotype
Oculofaciocardiodental syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 04, 2023 | This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 1633 of the BCOR protein (p.Ser1633Leu). This variant is present in population databases (rs754470140, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with BCOR-related conditions. ClinVar contains an entry for this variant (Variation ID: 2174174). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on BCOR 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:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at