rs142238093
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Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6BP7BS1
The NM_006086.4(TUBB3):c.1287G>A(p.Thr429=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000219 in 1,613,934 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 Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.00044 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00020 ( 0 hom. )
Consequence
TUBB3
NM_006086.4 synonymous
NM_006086.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -4.16
Genes affected
TUBB3 (HGNC:20772): (tubulin beta 3 class III) This gene encodes a class III member of the beta tubulin protein family. Beta tubulins are one of two core protein families (alpha and beta tubulins) that heterodimerize and assemble to form microtubules. This protein is primarily expressed in neurons and may be involved in neurogenesis and axon guidance and maintenance. Mutations in this gene are the cause of congenital fibrosis of the extraocular muscles type 3. Alternate splicing results in multiple transcript variants. A pseudogene of this gene is found on chromosome 6. [provided by RefSeq, Oct 2010]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -10 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.54).
BP6
Variant 16-89935738-G-A is Benign according to our data. Variant chr16-89935738-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 212498.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Benign=1, Uncertain_significance=1}.
BP7
Synonymous conserved (PhyloP=-4.16 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00044 (67/152362) while in subpopulation AFR AF= 0.00118 (49/41588). AF 95% confidence interval is 0.000915. There are 0 homozygotes in gnomad4. There are 32 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| TUBB3 | NM_006086.4 | c.1287G>A | p.Thr429= | synonymous_variant | 4/4 | ENST00000315491.12 | NP_006077.2 | |
| TUBB3 | NM_001197181.2 | c.1071G>A | p.Thr357= | synonymous_variant | 4/4 | NP_001184110.1 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| TUBB3 | ENST00000315491.12 | c.1287G>A | p.Thr429= | synonymous_variant | 4/4 | 1 | NM_006086.4 | ENSP00000320295 | P1 |
Frequencies
GnomAD3 genomes 0.000440 AC: 67AN: 152244Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000211 AC: 53AN: 251298Hom.: 0 AF XY: 0.000177 AC XY: 24AN XY: 135842
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GnomAD4 exome AF: 0.000196 AC: 286AN: 1461572Hom.: 0 Cov.: 32 AF XY: 0.000205 AC XY: 149AN XY: 727094
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GnomAD4 genome 0.000440 AC: 67AN: 152362Hom.: 0 Cov.: 33 AF XY: 0.000429 AC XY: 32AN XY: 74508
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:2
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not specified Uncertain:1Benign:1
| Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Jul 20, 2015 | - - |
| Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 08, 2016 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
not provided Benign:1
| Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Nov 02, 2023 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at