2-110638014-G-A
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2BP4_ModerateBS1_Supporting
The NM_004336.5(BUB1):c.3208C>T(p.Arg1070Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000157 in 1,593,842 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1070H) has been classified as Uncertain significance.
Frequency
Consequence
NM_004336.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BUB1 | NM_004336.5 | c.3208C>T | p.Arg1070Cys | missense_variant | 25/25 | ENST00000302759.11 | |
BUB1 | NM_001278616.2 | c.3148C>T | p.Arg1050Cys | missense_variant | 24/24 | ||
BUB1 | NM_001278617.2 | c.3037C>T | p.Arg1013Cys | missense_variant | 24/24 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BUB1 | ENST00000302759.11 | c.3208C>T | p.Arg1070Cys | missense_variant | 25/25 | 1 | NM_004336.5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000329 AC: 5AN: 152108Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000335 AC: 8AN: 238744Hom.: 0 AF XY: 0.0000387 AC XY: 5AN XY: 129196
GnomAD4 exome AF: 0.0000139 AC: 20AN: 1441616Hom.: 0 Cov.: 30 AF XY: 0.0000167 AC XY: 12AN XY: 716618
GnomAD4 genome AF: 0.0000328 AC: 5AN: 152226Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74412
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 10, 2022 | The p.R1070C variant (also known as c.3208C>T), located in coding exon 25 of the BUB1 gene, results from a C to T substitution at nucleotide position 3208. The arginine at codon 1070 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at