rs749945164
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Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 0P and 3B. BP4_ModerateBP7
The NM_006086.4(TUBB3):c.1023C>T(p.Phe341=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000124 in 1,614,122 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 (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000013 ( 0 hom. )
Consequence
TUBB3
NM_006086.4 synonymous
NM_006086.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.211
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 Likely_benign. Variant got -3 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.38).
BP7
?
Synonymous conserved (PhyloP=-0.211 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TUBB3 | NM_006086.4 | c.1023C>T | p.Phe341= | synonymous_variant | 4/4 | ENST00000315491.12 | |
TUBB3 | NM_001197181.2 | c.807C>T | p.Phe269= | synonymous_variant | 4/4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TUBB3 | ENST00000315491.12 | c.1023C>T | p.Phe341= | synonymous_variant | 4/4 | 1 | NM_006086.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152254Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251468Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135902
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GnomAD4 exome AF: 0.0000130 AC: 19AN: 1461868Hom.: 0 Cov.: 32 AF XY: 0.00000688 AC XY: 5AN XY: 727236
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GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152254Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74378
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Oct 05, 2015 | - - |
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