11-8038962-T-C
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The ENST00000305253.8(TUB):āc.89T>Cā(p.Met30Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000682 in 1,613,904 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M30I) has been classified as Uncertain significance.
Frequency
Consequence
ENST00000305253.8 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TUB | NM_003320.5 | c.89T>C | p.Met30Thr | missense_variant | 1/13 | ||
TUB | XM_005253109.4 | c.164+19604T>C | intron_variant | ||||
TUB | XM_047427512.1 | c.164+19604T>C | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TUB | ENST00000305253.8 | c.89T>C | p.Met30Thr | missense_variant | 1/13 | 1 | |||
ENST00000526646.2 | n.202+555A>G | intron_variant, non_coding_transcript_variant | 3 | ||||||
TUB | ENST00000534099.5 | c.56+19604T>C | intron_variant | 2 | |||||
ENST00000528151.1 | n.224A>G | non_coding_transcript_exon_variant | 2/2 | 4 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152108Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000795 AC: 2AN: 251442Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135892
GnomAD4 exome AF: 0.00000616 AC: 9AN: 1461796Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2AN XY: 727200
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152108Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74294
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | May 03, 2022 | This sequence change replaces methionine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 30 of the TUB protein (p.Met30Thr). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with TUB-related conditions. 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. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at