6-70216988-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001851.6(COL9A1):c.2675C>T(p.Pro892Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000173 in 1,613,974 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. P892P) has been classified as Likely benign.
Frequency
Consequence
NM_001851.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL9A1 | NM_001851.6 | c.2675C>T | p.Pro892Leu | missense_variant | 38/38 | ENST00000357250.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL9A1 | ENST00000357250.11 | c.2675C>T | p.Pro892Leu | missense_variant | 38/38 | 1 | NM_001851.6 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000394 AC: 6AN: 152140Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000320 AC: 8AN: 249942Hom.: 0 AF XY: 0.0000296 AC XY: 4AN XY: 135286
GnomAD4 exome AF: 0.0000150 AC: 22AN: 1461834Hom.: 0 Cov.: 31 AF XY: 0.0000193 AC XY: 14AN XY: 727208
GnomAD4 genome AF: 0.0000394 AC: 6AN: 152140Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74308
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 07, 2022 | This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 892 of the COL9A1 protein (p.Pro892Leu). This variant is present in population databases (rs760617713, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with COL9A1-related conditions. ClinVar contains an entry for this variant (Variation ID: 593645). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt COL9A1 protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Sep 01, 2017 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at