chr17-72123592-G-GC
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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
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Calibrated prediction
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Prediction
Splicing
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Calibrated prediction
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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