rs587776541
Positions:
Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_000346.4(SOX9):c.736dup(p.Gln246ProfsTer6) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: not found (cov: 32)
Consequence
SOX9
NM_000346.4 frameshift
NM_000346.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 3.63
Genes affected
SOX9 (HGNC:11204): (SRY-box transcription factor 9) The protein encoded by this gene recognizes the sequence CCTTGAG along with other members of the HMG-box class DNA-binding proteins. It acts during chondrocyte differentiation and, with steroidogenic factor 1, regulates transcription of the anti-Muellerian hormone (AMH) gene. Deficiencies lead to the skeletal malformation syndrome campomelic dysplasia, frequently with sex reversal. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 11 ACMG points.
PVS1
?
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. There are 36 pathogenic variants in the truncated region.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 17-72123592-G-GC is Pathogenic according to our data. Variant chr17-72123592-G-GC is described in ClinVar as [Pathogenic]. Clinvar id is 2509.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SOX9 | NM_000346.4 | c.736dup | p.Gln246ProfsTer6 | frameshift_variant | 3/3 | ENST00000245479.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SOX9 | ENST00000245479.3 | c.736dup | p.Gln246ProfsTer6 | frameshift_variant | 3/3 | 1 | NM_000346.4 | P1 | |
SOX9-AS1 | ENST00000414600.1 | n.96+18092_96+18093insG | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Cov.: 43
GnomAD4 exome
Cov.:
43
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:2
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Campomelic dysplasia with autosomal sex reversal Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Oct 01, 1996 | - - |
Camptomelic dysplasia Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Oct 01, 1996 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at