1-204117128-A-G

Position:

• chr1-204117128-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.48

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]

ACMG classification

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	UniProt
SOX13	NM_005686.3	c.598A>G	p.Lys200Glu	missense_variant	6/14	ENST00000367204.6
SOX13	XM_047435006.1	c.598A>G	p.Lys200Glu	missense_variant	6/14
SOX13	XM_005245623.4	c.598A>G	p.Lys200Glu	missense_variant	6/14
SOX13	XM_047435007.1	c.598A>G	p.Lys200Glu	missense_variant	6/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SOX13	ENST00000367204.6	c.598A>G	p.Lys200Glu	missense_variant	6/14	1	NM_005686.3	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

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 28, 2024

The 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
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;