chr1-85270626-T-A
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_003921.5(BCL10):c.338A>T(p.His113Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000752 in 1,595,200 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_003921.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BCL10 | NM_003921.5 | c.338A>T | p.His113Leu | missense_variant | 2/3 | ENST00000648566.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BCL10 | ENST00000648566.1 | c.338A>T | p.His113Leu | missense_variant | 2/3 | NM_003921.5 | P1 | ||
BCL10 | ENST00000620248.3 | c.338A>T | p.His113Leu | missense_variant | 2/3 | 5 | |||
BCL10 | ENST00000649434.1 | n.404A>T | non_coding_transcript_exon_variant | 2/3 | |||||
BCL10 | ENST00000650582.1 | n.869A>T | non_coding_transcript_exon_variant | 2/3 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152220Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000254 AC: 6AN: 236526Hom.: 0 AF XY: 0.0000313 AC XY: 4AN XY: 127912
GnomAD4 exome AF: 0.00000693 AC: 10AN: 1442980Hom.: 0 Cov.: 30 AF XY: 0.00000696 AC XY: 5AN XY: 717992
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152220Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74374
ClinVar
Submissions by phenotype
Immunodeficiency 37 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 23, 2018 | In summary, this variant has uncertain impact on BCL10 function. The available evidence is currently insufficient to determine its role 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with a BCL10-related disease. This variant is present in population databases (rs775016059, ExAC 0.01%). This sequence change replaces histidine with leucine at codon 113 of the BCL10 protein (p.His113Leu). The histidine residue is moderately conserved and there is a moderate physicochemical difference between histidine and leucine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at