rs61743676
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Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2
The ENST00000315491.12(TUBB3):c.666C>T(p.Tyr222=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00201 in 1,614,164 control chromosomes in the GnomAD database, including 72 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0012 ( 7 hom., cov: 33)
Exomes 𝑓: 0.0021 ( 65 hom. )
Consequence
TUBB3
ENST00000315491.12 synonymous
ENST00000315491.12 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.40
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 -19 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.44).
BP6
Variant 16-89935117-C-T is Benign according to our data. Variant chr16-89935117-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 160194.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-89935117-C-T is described in Lovd as [Benign].
BP7
Synonymous conserved (PhyloP=-1.4 with no splicing effect.
BS1
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00116 (176/152340) while in subpopulation SAS AF= 0.0294 (142/4826). AF 95% confidence interval is 0.0255. There are 7 homozygotes in gnomad4. There are 110 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 7 AD,AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TUBB3 | NM_006086.4 | c.666C>T | p.Tyr222= | synonymous_variant | 4/4 | ENST00000315491.12 | NP_006077.2 | |
TUBB3 | NM_001197181.2 | c.450C>T | p.Tyr150= | synonymous_variant | 4/4 | NP_001184110.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TUBB3 | ENST00000315491.12 | c.666C>T | p.Tyr222= | synonymous_variant | 4/4 | 1 | NM_006086.4 | ENSP00000320295 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00117 AC: 178AN: 152222Hom.: 7 Cov.: 33
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GnomAD3 exomes AF: 0.00417 AC: 1049AN: 251434Hom.: 30 AF XY: 0.00564 AC XY: 767AN XY: 135910
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GnomAD4 exome AF: 0.00209 AC: 3062AN: 1461824Hom.: 65 Cov.: 31 AF XY: 0.00306 AC XY: 2226AN XY: 727210
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GnomAD4 genome AF: 0.00116 AC: 176AN: 152340Hom.: 7 Cov.: 33 AF XY: 0.00148 AC XY: 110AN XY: 74496
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:7
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:3
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Feb 20, 2014 | - - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
not provided Benign:3
Likely benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Dec 15, 2023 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 19, 2019 | - - |
TUBB3-related disorder Benign:1
Benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Jun 17, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at