chr10-68882108-C-T
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_152709.5(STOX1):c.461C>T(p.Pro154Leu) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.0000886 in 1,613,364 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 2/3 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. P154S) has been classified as Uncertain significance.
Frequency
Consequence
NM_152709.5 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
STOX1 | NM_152709.5 | c.461C>T | p.Pro154Leu | missense_variant, splice_region_variant | 2/4 | ENST00000298596.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
STOX1 | ENST00000298596.11 | c.461C>T | p.Pro154Leu | missense_variant, splice_region_variant | 2/4 | 1 | NM_152709.5 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.000105 AC: 16AN: 152152Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000842 AC: 21AN: 249430Hom.: 0 AF XY: 0.0000813 AC XY: 11AN XY: 135336
GnomAD4 exome AF: 0.0000869 AC: 127AN: 1461212Hom.: 0 Cov.: 31 AF XY: 0.0000922 AC XY: 67AN XY: 726946
GnomAD4 genome ? AF: 0.000105 AC: 16AN: 152152Hom.: 0 Cov.: 32 AF XY: 0.000161 AC XY: 12AN XY: 74316
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 07, 2022 | The c.461C>T (p.P154L) alteration is located in exon 2 (coding exon 2) of the STOX1 gene. This alteration results from a C to T substitution at nucleotide position 461, causing the proline (P) at amino acid position 154 to be replaced by a leucine (L). 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