chr1-204113075-G-A

Position:

• chr1-204113075-G-A

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_005686.3(SOX13):​c.160G>A​(p.Ala54Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000621 in 1,448,540 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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)
  • Exomes 𝑓: 0.0000062 (0 hom.)
• Consequence: SOX13 NM_005686.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.448

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 Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.08729255).
• BS2: High AC in GnomAdExome4 at 9 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SOX13	NM_005686.3	c.160G>A	p.Ala54Thr	missense_variant	2/14	ENST00000367204.6	NP_005677.2
SOX13	XM_047435006.1	c.160G>A	p.Ala54Thr	missense_variant	2/14		XP_047290962.1
SOX13	XM_005245623.4	c.160G>A	p.Ala54Thr	missense_variant	2/14		XP_005245680.1
SOX13	XM_047435007.1	c.160G>A	p.Ala54Thr	missense_variant	2/14		XP_047290963.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SOX13	ENST00000367204.6	c.160G>A	p.Ala54Thr	missense_variant	2/14	1	NM_005686.3	ENSP00000356172	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000621 AC: 9 AN: 1448540 Hom.: 0 Cov.: 32 AF XY: 0.00000695 AC XY: 5 AN XY: 719412

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: 0.00000723

Gnomad4 OTH exome AF: 0.0000167

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

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

Jan 24, 2024

The c.160G>A (p.A54T) alteration is located in exon 2 (coding exon 1) of the SOX13 gene. This alteration results from a G to A substitution at nucleotide position 160, causing the alanine (A) at amino acid position 54 to be replaced by a threonine (T). 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	0.071
BayesDel_addAF	Uncertain	0.055	T
BayesDel_noAF	Benign	-0.16
CADD	Benign	8.0
DANN	Benign	0.97
DEOGEN2	Benign	0.10	T;T;T;T
Eigen	Benign	-0.67
Eigen_PC	Benign	-0.61
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.60	.;T;T;T
M_CAP	Benign	0.068	D
MetaRNN	Benign	0.087	T;T;T;T
MetaSVM	Uncertain	0.16	D
MutationAssessor	Benign	0.34	N;.;.;N
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.14	N;N;N;.
REVEL	Benign	0.22
Sift	Benign	0.11	T;T;T;.
Sift4G	Benign	0.61	T;T;T;T
Polyphen		0.0	B;.;.;B
Vest4		0.055
MutPred		0.089		Gain of phosphorylation at A54 (P = 0.0055);Gain of phosphorylation at A54 (P = 0.0055);Gain of phosphorylation at A54 (P = 0.0055);Gain of phosphorylation at A54 (P = 0.0055);
MVP		0.44
MPC		0.027
ClinPred		0.11	T
GERP RS		2.7
Varity_R		0.060
gMVP		0.070

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs973690946; hg19: chr1-204082203;