chr17-72121452-GC-G
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_000346.4(SOX9):c.66del(p.Ser23AlafsTer38) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★).
Frequency
Genomes: not found (cov: 31)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
SOX9
NM_000346.4 frameshift
NM_000346.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 4.77
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 12 ACMG points.
PVS1
?
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 113 pathogenic variants in the truncated region.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 17-72121452-GC-G is Pathogenic according to our data. Variant chr17-72121452-GC-G is described in ClinVar as [Likely_pathogenic]. Clinvar id is 3032236.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SOX9 | NM_000346.4 | c.66del | p.Ser23AlafsTer38 | frameshift_variant | 1/3 | ENST00000245479.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SOX9 | ENST00000245479.3 | c.66del | p.Ser23AlafsTer38 | frameshift_variant | 1/3 | 1 | NM_000346.4 | P1 | |
SOX9-AS1 | ENST00000414600.1 | n.96+20232del | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes ? Cov.: 31
GnomAD3 genomes
?
Cov.:
31
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1460508Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 726602
GnomAD4 exome
Data not reliable, filtered out with message: AC0
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1460508
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31
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0
AN XY:
726602
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GnomAD4 genome ? Cov.: 31
GnomAD4 genome
?
Cov.:
31
ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
SOX9-related disorder Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jan 05, 2024 | The SOX9 c.66delC variant is predicted to result in a frameshift and premature protein termination (p.Ser23Alafs*38). To our knowledge, this variant has not been reported in the literature in association with SOX9-related condition(s) or in a large population database, indicating this variant is rare. Frameshift variants in SOX9 are expected to be pathogenic. This variant is interpreted as likely pathogenic. - |
Computational scores
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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
Publications
No publications associated with this variant yet.