15-73887735-T-C
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_153356.3(TBC1D21):āc.893T>Cā(p.Leu298Pro) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,460,558 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 13/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Consequence
NM_153356.3 missense, splice_region
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 |
---|---|---|---|---|---|---|---|
TBC1D21 | NM_153356.3 | c.893T>C | p.Leu298Pro | missense_variant, splice_region_variant | 9/11 | ENST00000300504.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TBC1D21 | ENST00000300504.7 | c.893T>C | p.Leu298Pro | missense_variant, splice_region_variant | 9/11 | 1 | NM_153356.3 | P1 | |
TBC1D21 | ENST00000535547.6 | c.785T>C | p.Leu262Pro | missense_variant, splice_region_variant | 8/10 | 1 | |||
TBC1D21 | ENST00000562056.1 | c.782T>C | p.Leu261Pro | missense_variant, splice_region_variant | 8/10 | 5 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 exome AF: 0.00000411 AC: 6AN: 1460558Hom.: 0 Cov.: 31 AF XY: 0.00000551 AC XY: 4AN XY: 726556
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 28, 2024 | The c.893T>C (p.L298P) alteration is located in exon 9 (coding exon 9) of the TBC1D21 gene. This alteration results from a T to C substitution at nucleotide position 893, causing the leucine (L) at amino acid position 298 to be replaced by a proline (P). 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
Publications
No publications associated with this variant yet.