1-204123798-A-G
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Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP3BS2
The NM_005686.3(SOX13):āc.1369A>Gā(p.Ile457Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000409 in 1,613,992 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.000026 ( 0 hom., cov: 33)
Exomes š: 0.000042 ( 0 hom. )
Consequence
SOX13
NM_005686.3 missense
NM_005686.3 missense
Scores
11
5
2
Clinical Significance
Conservation
PhyloP100: 9.32
Genes affected
SOX13 (HGNC:11192): (SRY-box transcription factor 13) 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 cell fate. The encoded protein may act as a transcriptional regulator after forming a protein complex with other proteins. It has also been determined to be a type-1 diabetes autoantigen, also known as islet cell antibody 12. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -3 ACMG points.
PP3
MetaRNN computational evidence supports a deleterious effect, 0.808
BS2
High AC in GnomAdExome4 at 62 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SOX13 | NM_005686.3 | c.1369A>G | p.Ile457Val | missense_variant | 12/14 | ENST00000367204.6 | |
SOX13 | XM_047435006.1 | c.1369A>G | p.Ile457Val | missense_variant | 12/14 | ||
SOX13 | XM_005245623.4 | c.1366A>G | p.Ile456Val | missense_variant | 12/14 | ||
SOX13 | XM_047435007.1 | c.1366A>G | p.Ile456Val | missense_variant | 12/14 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SOX13 | ENST00000367204.6 | c.1369A>G | p.Ile457Val | missense_variant | 12/14 | 1 | NM_005686.3 | P1 | |
SOX13 | ENST00000618875.4 | c.1369A>G | p.Ile457Val | missense_variant | 11/13 | 1 | P1 | ||
SOX13 | ENST00000272193.10 | n.1236A>G | non_coding_transcript_exon_variant | 9/11 | 2 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152172Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000120 AC: 3AN: 250464Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135722
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GnomAD4 exome AF: 0.0000424 AC: 62AN: 1461820Hom.: 0 Cov.: 32 AF XY: 0.0000371 AC XY: 27AN XY: 727222
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GnomAD4 genome AF: 0.0000263 AC: 4AN: 152172Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74324
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 05, 2023 | The c.1369A>G (p.I457V) alteration is located in exon 12 (coding exon 11) of the SOX13 gene. This alteration results from a A to G substitution at nucleotide position 1369, causing the isoleucine (I) at amino acid position 457 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Uncertain
D;D
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D
MetaSVM
Pathogenic
D
MutationAssessor
Uncertain
M;M
MutationTaster
Benign
D
PrimateAI
Pathogenic
D
PROVEAN
Benign
N;.
REVEL
Pathogenic
Sift
Uncertain
D;.
Sift4G
Pathogenic
D;D
Polyphen
D;D
Vest4
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_DG_spliceai
Position offset: -1
Find out detailed SpliceAI scores and Pangolin per-transcript scores at