rs201572795
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 3P and 5B. PM2PP3BP6BS1
The NM_001853.4(COL9A3):c.1621G>A(p.Ala541Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00027 in 1,613,292 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A541V) has been classified as Uncertain significance.
Frequency
Consequence
NM_001853.4 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 |
---|---|---|---|---|---|---|---|
COL9A3 | NM_001853.4 | c.1621G>A | p.Ala541Thr | missense_variant | 30/32 | ENST00000649368.1 | |
COL9A3 | XM_047439893.1 | c.1798G>A | p.Ala600Thr | missense_variant | 29/31 | ||
COL9A3 | XM_047439894.1 | c.1060G>A | p.Ala354Thr | missense_variant | 30/32 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL9A3 | ENST00000649368.1 | c.1621G>A | p.Ala541Thr | missense_variant | 30/32 | NM_001853.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000112 AC: 17AN: 152188Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000104 AC: 26AN: 250372Hom.: 0 AF XY: 0.000133 AC XY: 18AN XY: 135496
GnomAD4 exome AF: 0.000286 AC: 418AN: 1461104Hom.: 0 Cov.: 31 AF XY: 0.000289 AC XY: 210AN XY: 726878
GnomAD4 genome AF: 0.000112 AC: 17AN: 152188Hom.: 0 Cov.: 33 AF XY: 0.000135 AC XY: 10AN XY: 74348
ClinVar
Submissions by phenotype
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Dec 07, 2020 | - - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 06, 2021 | The c.1621G>A (p.A541T) alteration is located in exon 30 (coding exon 30) of the COL9A3 gene. This alteration results from a G to A substitution at nucleotide position 1621, causing the alanine (A) at amino acid position 541 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
COL9A3-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jan 24, 2023 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at