chrX-40062248-G-A
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The ENST00000378444.9(BCOR):c.4319C>T(p.Pro1440Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000024 in 1,209,263 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 10 hemizygotes in GnomAD. In-silico tool predicts 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. P1440P) has been classified as Likely benign.
Frequency
Consequence
ENST00000378444.9 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
BCOR | NM_001123385.2 | c.4319C>T | p.Pro1440Leu | missense_variant | 10/15 | ENST00000378444.9 | NP_001116857.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
BCOR | ENST00000378444.9 | c.4319C>T | p.Pro1440Leu | missense_variant | 10/15 | 1 | NM_001123385.2 | ENSP00000367705 | P2 |
Frequencies
GnomAD3 genomes AF: 0.0000269 AC: 3AN: 111513Hom.: 0 Cov.: 22 AF XY: 0.0000297 AC XY: 1AN XY: 33669
GnomAD3 exomes AF: 0.0000111 AC: 2AN: 180605Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 65547
GnomAD4 exome AF: 0.0000237 AC: 26AN: 1097750Hom.: 0 Cov.: 33 AF XY: 0.0000248 AC XY: 9AN XY: 363136
GnomAD4 genome AF: 0.0000269 AC: 3AN: 111513Hom.: 0 Cov.: 22 AF XY: 0.0000297 AC XY: 1AN XY: 33669
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 16, 2024 | The c.4319C>T (p.P1440L) alteration is located in exon 10 (coding exon 9) of the BCOR gene. This alteration results from a C to T substitution at nucleotide position 4319, causing the proline (P) at amino acid position 1440 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Oculofaciocardiodental syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jun 13, 2022 | This missense change has been observed in individual(s) with BCOR-related conditions (Invitae). 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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C65"). ClinVar contains an entry for this variant (Variation ID: 579723). This missense change has been observed in at least one individual who was not affected with BCOR-related conditions (Invitae). This variant is present in population databases (no rsID available, gnomAD 0.006%). This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 1406 of the BCOR protein (p.Pro1406Leu). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at