chr22-18121480-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.
The NM_018943.3(TUBA8):c.5G>A(p.Arg2Gln) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000266 in 1,613,738 control chromosomes in the GnomAD database, with no homozygous occurrence. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R2W) has been classified as Uncertain significance.
Frequency
Consequence
NM_018943.3 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TUBA8 | NM_018943.3 | c.5G>A | p.Arg2Gln | missense_variant, splice_region_variant | 2/5 | ENST00000330423.8 | |
TUBA8 | NM_001193414.2 | c.-194G>A | splice_region_variant, 5_prime_UTR_variant | 2/5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TUBA8 | ENST00000330423.8 | c.5G>A | p.Arg2Gln | missense_variant, splice_region_variant | 2/5 | 1 | NM_018943.3 | P1 | |
ENST00000623543.1 | n.9675C>T | non_coding_transcript_exon_variant | 1/1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000657 AC: 10AN: 152160Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000239 AC: 6AN: 251336Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135866
GnomAD4 exome AF: 0.0000226 AC: 33AN: 1461578Hom.: 0 Cov.: 30 AF XY: 0.0000206 AC XY: 15AN XY: 727092
GnomAD4 genome ? AF: 0.0000657 AC: 10AN: 152160Hom.: 0 Cov.: 32 AF XY: 0.0000673 AC XY: 5AN XY: 74328
ClinVar
Submissions by phenotype
Polymicrogyria with optic nerve hypoplasia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | Apr 19, 2018 | This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Nov 03, 2022 | 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 1033914). This variant has not been reported in the literature in individuals affected with TUBA8-related conditions. This variant is present in population databases (rs761087286, gnomAD 0.006%). This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 2 of the TUBA8 protein (p.Arg2Gln). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at