1-204114339-G-T

Position:

• chr1-204114339-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005686.3(SOX13):​c.238G>T​(p.Gly80Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SOX13 NM_005686.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.890

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07161933).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SOX13	NM_005686.3	c.238G>T	p.Gly80Cys	missense_variant	3/14	ENST00000367204.6	NP_005677.2
SOX13	XM_047435006.1	c.238G>T	p.Gly80Cys	missense_variant	3/14		XP_047290962.1
SOX13	XM_005245623.4	c.238G>T	p.Gly80Cys	missense_variant	3/14		XP_005245680.1
SOX13	XM_047435007.1	c.238G>T	p.Gly80Cys	missense_variant	3/14		XP_047290963.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SOX13	ENST00000367204.6	c.238G>T	p.Gly80Cys	missense_variant	3/14	1	NM_005686.3	ENSP00000356172.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1455214 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 723360

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

Bravo AF: 0.0000113

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

Nov 17, 2023

The c.238G>T (p.G80C) alteration is located in exon 3 (coding exon 2) of the SOX13 gene. This alteration results from a G to T substitution at nucleotide position 238, causing the glycine (G) at amino acid position 80 to be replaced by a cysteine (C). 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	Benign	0.074
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Benign	-0.090
CADD	Benign	20
DANN	Benign	0.97
DEOGEN2	Benign	0.13	T;T;T
Eigen	Benign	-0.78
Eigen_PC	Benign	-0.82
FATHMM_MKL	Benign	0.040	N
LIST_S2	Benign	0.68	.;T;T
M_CAP	Uncertain	0.24	D
MetaRNN	Benign	0.072	T;T;T
MetaSVM	Uncertain	0.24	D
MutationAssessor	Benign	0.0	N;.;N
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-1.1	N;N;.
REVEL	Uncertain	0.36
Sift	Uncertain	0.0050	D;D;.
Sift4G	Uncertain	0.019	D;D;D
Polyphen		0.42	B;.;B
Vest4		0.29
MutPred		0.10		Loss of sheet (P = 0.1907);Loss of sheet (P = 0.1907);Loss of sheet (P = 0.1907);
MVP		0.19
MPC		0.029
ClinPred		0.20	T
GERP RS		2.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.14
gMVP		0.062

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs1406386033; hg19: chr1-204083467;