2-101022430-A-G
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_001330348.2(TBC1D8):c.2612T>C(p.Ile871Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000682 in 1,613,208 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I871V) has been classified as Uncertain significance.
Frequency
Consequence
NM_001330348.2 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 |
---|---|---|---|---|---|---|---|
TBC1D8 | NM_001330348.2 | c.2612T>C | p.Ile871Thr | missense_variant | 16/20 | ENST00000409318.2 | |
TBC1D8 | NM_001102426.3 | c.2567T>C | p.Ile856Thr | missense_variant | 16/20 | ||
TBC1D8 | NR_138475.2 | n.2578T>C | non_coding_transcript_exon_variant | 15/19 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TBC1D8 | ENST00000409318.2 | c.2612T>C | p.Ile871Thr | missense_variant | 16/20 | 5 | NM_001330348.2 | A1 | |
TBC1D8 | ENST00000376840.8 | c.2567T>C | p.Ile856Thr | missense_variant | 16/20 | 1 | P4 | ||
RPL31 | ENST00000441435.1 | c.310-1195A>G | intron_variant | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000460 AC: 7AN: 152234Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000807 AC: 2AN: 247956Hom.: 0 AF XY: 0.00000743 AC XY: 1AN XY: 134630
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1460974Hom.: 0 Cov.: 33 AF XY: 0.00000275 AC XY: 2AN XY: 726756
GnomAD4 genome ? AF: 0.0000460 AC: 7AN: 152234Hom.: 0 Cov.: 32 AF XY: 0.0000807 AC XY: 6AN XY: 74368
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | May 15, 2023 | The c.2567T>C (p.I856T) alteration is located in exon 16 (coding exon 16) of the TBC1D8 gene. This alteration results from a T to C substitution at nucleotide position 2567, causing the isoleucine (I) at amino acid position 856 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at