chr2-101022431-T-C
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_001330348.2(TBC1D8):āc.2611A>Gā(p.Ile871Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000539 in 1,613,314 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign 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. I871T) has been classified as Uncertain significance.
Frequency
Consequence
NM_001330348.2 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TBC1D8 | NM_001330348.2 | c.2611A>G | p.Ile871Val | missense_variant | 16/20 | ENST00000409318.2 | |
TBC1D8 | NM_001102426.3 | c.2566A>G | p.Ile856Val | missense_variant | 16/20 | ||
TBC1D8 | NR_138475.2 | n.2577A>G | non_coding_transcript_exon_variant | 15/19 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TBC1D8 | ENST00000409318.2 | c.2611A>G | p.Ile871Val | missense_variant | 16/20 | 5 | NM_001330348.2 | A1 | |
TBC1D8 | ENST00000376840.8 | c.2566A>G | p.Ile856Val | missense_variant | 16/20 | 1 | P4 | ||
RPL31 | ENST00000441435.1 | c.310-1194T>C | intron_variant | 2 |
Frequencies
GnomAD3 genomes AF: 0.0000722 AC: 11AN: 152258Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000101 AC: 25AN: 247894Hom.: 0 AF XY: 0.000104 AC XY: 14AN XY: 134604
GnomAD4 exome AF: 0.0000520 AC: 76AN: 1460938Hom.: 1 Cov.: 33 AF XY: 0.0000647 AC XY: 47AN XY: 726748
GnomAD4 genome AF: 0.0000722 AC: 11AN: 152376Hom.: 0 Cov.: 32 AF XY: 0.0000805 AC XY: 6AN XY: 74520
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 21, 2024 | The c.2566A>G (p.I856V) alteration is located in exon 16 (coding exon 16) of the TBC1D8 gene. This alteration results from a A to G substitution at nucleotide position 2566, causing the isoleucine (I) at amino acid position 856 to be replaced by a valine (V). 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