chr12-23536546-G-T
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PP2PP5_Moderate
The NM_006940.6(SOX5):c.1895C>A(p.Thr632Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★).
Frequency
Genomes: not found (cov: 32)
Consequence
SOX5
NM_006940.6 missense
NM_006940.6 missense
Scores
6
10
3
Clinical Significance
Conservation
PhyloP100: 9.98
Genes affected
SOX5 (HGNC:11201): (SRY-box transcription factor 5) This gene encodes a member of the SOX (SRY-related HMG-box) family of transcription factors involved in the regulation of embryonic development and in the determination of the cell fate. The encoded protein may act as a transcriptional regulator after forming a protein complex with other proteins. The encoded protein may play a role in chondrogenesis. A pseudogene of this gene is located on chromosome 8. Multiple transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 5 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP2
Missense variant in gene, where missense usually causes diseases (based on misZ statistic), SOX5. . Gene score misZ 3.1513 (greater than the threshold 3.09). Trascript score misZ 3.799 (greater than threshold 3.09). GenCC has associacion of gene with Lamb-Shaffer syndrome, developmental and speech delay due to SOX5 deficiency.
PP5
Variant 12-23536546-G-T is Pathogenic according to our data. Variant chr12-23536546-G-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 431148.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SOX5 | NM_006940.6 | c.1895C>A | p.Thr632Asn | missense_variant | 14/15 | ENST00000451604.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SOX5 | ENST00000451604.7 | c.1895C>A | p.Thr632Asn | missense_variant | 14/15 | 1 | NM_006940.6 | A1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Cov.: 32
GnomAD4 exome
Cov.:
32
GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:1Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Lamb-Shaffer syndrome Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Groupe Hospitalier Pitie Salpetriere, UF Genomique du Developpement, Assistance Publique Hopitaux de Paris | Jan 06, 2017 | autism with no language; tall stature; macrocephaly - |
Intellectual disability Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | Institute for Human Genetics, University Hospital Essen | Aug 05, 2019 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Uncertain
.;.;D;T;.;.;.;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D;D;.;.;D;D
M_CAP
Benign
T
MetaRNN
Uncertain
D;D;D;D;D;D;D;D
MetaSVM
Uncertain
T
MutationAssessor
Uncertain
.;.;M;.;.;.;.;.
MutationTaster
Benign
D;D;D;D;D;D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
D;D;D;D;D;.;D;D
REVEL
Uncertain
Sift
Uncertain
D;D;D;D;D;.;D;D
Sift4G
Pathogenic
D;D;D;D;D;.;D;D
Polyphen
0.99, 1.0, 1.0
.;D;D;.;D;D;D;.
Vest4
MutPred
0.33
.;.;Gain of catalytic residue at P627 (P = 0);.;.;.;.;.;
MVP
MPC
3.0
ClinPred
D
GERP RS
Varity_R
gMVP
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