12-57716415-C-T
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_006812.4(OS9):c.896C>T(p.Ala299Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000122 in 1,553,786 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign 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. A299S) has been classified as Uncertain significance.
Frequency
Consequence
NM_006812.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
OS9 | NM_006812.4 | c.896C>T | p.Ala299Val | missense_variant | 8/15 | ENST00000315970.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
OS9 | ENST00000315970.12 | c.896C>T | p.Ala299Val | missense_variant | 8/15 | 1 | NM_006812.4 | P4 | |
ENST00000549477.1 | n.534+4562G>A | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.00000658 AC: 1AN: 152030Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000308 AC: 5AN: 162104Hom.: 0 AF XY: 0.0000469 AC XY: 4AN XY: 85228
GnomAD4 exome AF: 0.0000128 AC: 18AN: 1401756Hom.: 0 Cov.: 31 AF XY: 0.00000723 AC XY: 5AN XY: 691744
GnomAD4 genome ? AF: 0.00000658 AC: 1AN: 152030Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 74252
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 30, 2021 | The c.896C>T (p.A299V) alteration is located in exon 8 (coding exon 8) of the OS9 gene. This alteration results from a C to T substitution at nucleotide position 896, causing the alanine (A) at amino acid position 299 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