1-204112935-T-A

Variant summary

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

The NM_005686.3(SOX13):c.20T>A(p.Ile7Asn) 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: 33)
• Consequence: SOX13 NM_005686.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.17

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=0.09505156).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SOX13	NM_005686.3	c.20T>A	p.Ile7Asn	missense_variant	2/14	ENST00000367204.6
SOX13	XM_047435006.1	c.20T>A	p.Ile7Asn	missense_variant	2/14
SOX13	XM_005245623.4	c.20T>A	p.Ile7Asn	missense_variant	2/14
SOX13	XM_047435007.1	c.20T>A	p.Ile7Asn	missense_variant	2/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SOX13	ENST00000367204.6	c.20T>A	p.Ile7Asn	missense_variant	2/14	1	NM_005686.3	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

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

May 30, 2023

The c.20T>A (p.I7N) alteration is located in exon 2 (coding exon 1) of the SOX13 gene. This alteration results from a T to A substitution at nucleotide position 20, causing the isoleucine (I) at amino acid position 7 to be replaced by an asparagine (N). 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	0.067
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Benign	-0.090
Cadd	Benign	19
Dann	Uncertain	0.98
DEOGEN2	Benign	0.11	T;T;T;T
Eigen	Benign	-0.45
Eigen_PC	Benign	-0.32
FATHMM_MKL	Benign	0.49	N
M_CAP	Benign	0.066	D
MetaRNN	Benign	0.095	T;T;T;T
MetaSVM	Uncertain	0.12	D
MutationAssessor	Benign	0.34	N;.;.;N
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.46	N;N;N;.
REVEL	Uncertain	0.30
Sift	Benign	0.046	D;T;D;.
Sift4G	Benign	0.34	T;T;T;T
Polyphen		0.0010	B;.;.;B
Vest4		0.19
MutPred		0.24		Gain of relative solvent accessibility (P = 0.005);Gain of relative solvent accessibility (P = 0.005);Gain of relative solvent accessibility (P = 0.005);Gain of relative solvent accessibility (P = 0.005);
MVP		0.43
MPC		0.041
ClinPred		0.15	T
GERP RS		1.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.065
gMVP		0.12

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-204082063;