rs117347229
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_001853.4(COL9A3):c.346-22G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0988 in 1,612,528 control chromosomes in the GnomAD database, including 8,618 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). There are indicators that this mutation may affect the branch point..
Frequency
Genomes: 𝑓 0.086 ( 678 hom., cov: 33)
Exomes 𝑓: 0.10 ( 7940 hom. )
Consequence
COL9A3
NM_001853.4 intron
NM_001853.4 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.09
Genes affected
COL9A3 (HGNC:2219): (collagen type IX alpha 3 chain) This gene encodes one of the three alpha chains of type IX collagen, the major collagen component of hyaline cartilage. Type IX collagen, a heterotrimeric molecule, is usually found in tissues containing type II collagen, a fibrillar collagen. Mutations in this gene are associated with multiple epiphyseal dysplasia type 3. [provided by RefSeq, Jan 2010]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
?
This place is a probable branch point but rather VUS (scored 4 / 10). Computational evidence support a benign effect (BayesDel_noAF=-0.54).
BP6
?
Variant 20-62821485-G-A is Benign according to our data. Variant chr20-62821485-G-A is described in ClinVar as [Benign]. Clinvar id is 258423.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
?
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.109 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL9A3 | NM_001853.4 | c.346-22G>A | intron_variant | ENST00000649368.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL9A3 | ENST00000649368.1 | c.346-22G>A | intron_variant | NM_001853.4 | P1 | ||||
COL9A3 | ENST00000452372.2 | c.235-22G>A | intron_variant | 5 | |||||
COL9A3 | ENST00000477612.5 | n.342-22G>A | intron_variant, non_coding_transcript_variant | 3 | |||||
COL9A3 | ENST00000489045.5 | n.392-22G>A | intron_variant, non_coding_transcript_variant | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0863 AC: 13125AN: 152088Hom.: 680 Cov.: 33
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GnomAD3 exomes AF: 0.0910 AC: 22757AN: 249952Hom.: 1228 AF XY: 0.0968 AC XY: 13131AN XY: 135600
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GnomAD4 exome AF: 0.100 AC: 146200AN: 1460322Hom.: 7940 Cov.: 33 AF XY: 0.102 AC XY: 73987AN XY: 726468
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GnomAD4 genome ? AF: 0.0862 AC: 13113AN: 152206Hom.: 678 Cov.: 33 AF XY: 0.0864 AC XY: 6430AN XY: 74430
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 27, 2018 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
BranchPoint Hunter
?
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at