1-204117128-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_005686.3(SOX13):​c.598A>G​(p.Lys200Glu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

SOX13
NM_005686.3 missense

Scores

3
11
5

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.48
Variant links:
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 Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.39802635).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SOX13NM_005686.3 linkuse as main transcriptc.598A>G p.Lys200Glu missense_variant 6/14 ENST00000367204.6 NP_005677.2
SOX13XM_047435006.1 linkuse as main transcriptc.598A>G p.Lys200Glu missense_variant 6/14 XP_047290962.1
SOX13XM_005245623.4 linkuse as main transcriptc.598A>G p.Lys200Glu missense_variant 6/14 XP_005245680.1
SOX13XM_047435007.1 linkuse as main transcriptc.598A>G p.Lys200Glu missense_variant 6/14 XP_047290963.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SOX13ENST00000367204.6 linkuse as main transcriptc.598A>G p.Lys200Glu missense_variant 6/141 NM_005686.3 ENSP00000356172 P1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
32

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 submitterclinical testingAmbry GeneticsFeb 28, 2024The c.598A>G (p.K200E) alteration is located in exon 6 (coding exon 5) of the SOX13 gene. This alteration results from a A to G substitution at nucleotide position 598, causing the lysine (K) at amino acid position 200 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.94
BayesDel_addAF
Pathogenic
0.20
D
BayesDel_noAF
Uncertain
0.060
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.30
T;T
Eigen
Uncertain
0.38
Eigen_PC
Uncertain
0.41
FATHMM_MKL
Uncertain
0.85
D
LIST_S2
Uncertain
0.95
.;D
M_CAP
Uncertain
0.21
D
MetaRNN
Benign
0.40
T;T
MetaSVM
Pathogenic
0.99
D
MutationAssessor
Benign
1.6
L;L
MutationTaster
Benign
0.68
N
PrimateAI
Uncertain
0.77
T
PROVEAN
Benign
-2.2
N;.
REVEL
Uncertain
0.59
Sift
Uncertain
0.0040
D;.
Sift4G
Uncertain
0.013
D;D
Polyphen
0.95
P;P
Vest4
0.50
MutPred
0.27
Loss of MoRF binding (P = 0.001);Loss of MoRF binding (P = 0.001);
MVP
0.63
MPC
0.66
ClinPred
0.83
D
GERP RS
5.1
Varity_R
0.32
gMVP
0.64

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.040
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-204086256; API