11-8038922-G-A
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The ENST00000305253.8(TUB):c.49G>A(p.Glu17Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000297 in 1,613,750 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
ENST00000305253.8 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TUB | NM_003320.5 | c.49G>A | p.Glu17Lys | missense_variant | 1/13 | ||
TUB | XM_005253109.4 | c.164+19564G>A | intron_variant | ||||
TUB | XM_047427512.1 | c.164+19564G>A | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TUB | ENST00000305253.8 | c.49G>A | p.Glu17Lys | missense_variant | 1/13 | 1 | |||
ENST00000526646.2 | n.202+595C>T | intron_variant, non_coding_transcript_variant | 3 | ||||||
TUB | ENST00000534099.5 | c.56+19564G>A | intron_variant | 2 | |||||
ENST00000528151.1 | n.264C>T | non_coding_transcript_exon_variant | 2/2 | 4 |
Frequencies
GnomAD3 genomes AF: 0.0000329 AC: 5AN: 152084Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000318 AC: 8AN: 251428Hom.: 0 AF XY: 0.0000294 AC XY: 4AN XY: 135880
GnomAD4 exome AF: 0.0000294 AC: 43AN: 1461666Hom.: 0 Cov.: 31 AF XY: 0.0000289 AC XY: 21AN XY: 727126
GnomAD4 genome AF: 0.0000329 AC: 5AN: 152084Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3AN XY: 74250
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Mar 25, 2022 | This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 17 of the TUB protein (p.Glu17Lys). This variant is present in population databases (rs144469939, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with TUB-related conditions. ClinVar contains an entry for this variant (Variation ID: 956554). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The lysine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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