chrX-140503952-A-G
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Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2
The NM_005634.3(SOX3):āc.1109T>Cā(p.Met370Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000174 in 1,150,493 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.000028 ( 0 hom., 0 hem., cov: 23)
Exomes š: 0.000016 ( 0 hom. 2 hem. )
Consequence
SOX3
NM_005634.3 missense
NM_005634.3 missense
Scores
2
4
11
Clinical Significance
Conservation
PhyloP100: 4.58
Genes affected
SOX3 (HGNC:11199): (SRY-box transcription factor 3) 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. Mutations in this gene have been associated with X-linked cognitive disability with growth hormone deficiency. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -5 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.27839577).
BS2
High Hemizygotes in GnomAdExome4 at 2 XL gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SOX3 | NM_005634.3 | c.1109T>C | p.Met370Thr | missense_variant | 1/1 | ENST00000370536.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SOX3 | ENST00000370536.5 | c.1109T>C | p.Met370Thr | missense_variant | 1/1 | NM_005634.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000277 AC: 3AN: 108430Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0AN XY: 31822
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GnomAD3 exomes AF: 0.0000184 AC: 2AN: 108937Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 30839
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GnomAD4 exome AF: 0.0000163 AC: 17AN: 1042063Hom.: 0 Cov.: 31 AF XY: 0.00000605 AC XY: 2AN XY: 330347
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GnomAD4 genome AF: 0.0000277 AC: 3AN: 108430Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0AN XY: 31822
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jun 10, 2022 | This variant has not been reported in the literature in individuals affected with SOX3-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. This sequence change replaces methionine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 370 of the SOX3 protein (p.Met370Thr). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
DEOGEN2
Benign
T
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D
M_CAP
Pathogenic
D
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
L
MutationTaster
Benign
D
PrimateAI
Pathogenic
D
PROVEAN
Benign
N
REVEL
Uncertain
Sift
Benign
T
Sift4G
Benign
T
Polyphen
B
Vest4
MutPred
Gain of glycosylation at M370 (P = 8e-04);
MVP
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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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