rs12089381

chr1-204121886-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005686.3(SOX13):c.776-14T>C variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0506 in 1,597,756 control chromosomes in the GnomAD database, including 3,268 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.089 (1055 hom., cov: 32)
  • Exomes 𝑓: 0.047 (2213 hom.)
• Consequence: SOX13 NM_005686.3 splice_polypyrimidine_tract, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.226

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.209 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SOX13	NM_005686.3	c.776-14T>C		splice_polypyrimidine_tract_variant, intron_variant		ENST00000367204.6
SOX13	XM_005245623.4	c.773-14T>C		splice_polypyrimidine_tract_variant, intron_variant
SOX13	XM_047435006.1	c.776-14T>C		splice_polypyrimidine_tract_variant, intron_variant
SOX13	XM_047435007.1	c.773-14T>C		splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SOX13	ENST00000367204.6	c.776-14T>C		splice_polypyrimidine_tract_variant, intron_variant		1	NM_005686.3	P1
SOX13	ENST00000618875.4	c.776-14T>C		splice_polypyrimidine_tract_variant, intron_variant		1		P1
SOX13	ENST00000480326.1	c.374T>C	p.Leu125Pro	missense_variant, NMD_transcript_variant	4/6	5
SOX13	ENST00000272193.10	n.643-14T>C		splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0891 AC: 13557 AN: 152072 Hom.: 1054 Cov.: 32

Gnomad AFR AF: 0.213

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0602

Gnomad ASJ AF: 0.0571

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.0261

Gnomad FIN AF: 0.0161

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0457

Gnomad OTH AF: 0.0932

GnomAD3 exomes AF: 0.0464 AC: 11457 AN: 246716 Hom.: 494 AF XY: 0.0442 AC XY: 5921 AN XY: 134054

Gnomad AFR exome AF: 0.214

Gnomad AMR exome AF: 0.0343

Gnomad ASJ exome AF: 0.0589

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0269

Gnomad FIN exome AF: 0.0140

Gnomad NFE exome AF: 0.0454

Gnomad OTH exome AF: 0.0461

GnomAD4 exome AF: 0.0466 AC: 67317 AN: 1445566 Hom.: 2213 Cov.: 30 AF XY: 0.0456 AC XY: 32845 AN XY: 720064

Gnomad4 AFR exome AF: 0.225

Gnomad4 AMR exome AF: 0.0368

Gnomad4 ASJ exome AF: 0.0552

Gnomad4 EAS exome AF: 0.000101

Gnomad4 SAS exome AF: 0.0282

Gnomad4 FIN exome AF: 0.0149

Gnomad4 NFE exome AF: 0.0456

Gnomad4 OTH exome AF: 0.0525

GnomAD4 genome AF: 0.0893 AC: 13583 AN: 152190 Hom.: 1055 Cov.: 32 AF XY: 0.0857 AC XY: 6381 AN XY: 74418

Gnomad4 AFR AF: 0.213

Gnomad4 AMR AF: 0.0601

Gnomad4 ASJ AF: 0.0571

Gnomad4 EAS AF: 0.000579

Gnomad4 SAS AF: 0.0261

Gnomad4 FIN AF: 0.0161

Gnomad4 NFE AF: 0.0457

Gnomad4 OTH AF: 0.0922

Alfa AF: 0.0576 Hom.: 162

Bravo AF: 0.0994

Asia WGS AF: 0.0230 AC: 79 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
Cadd	Benign	11
Dann	Benign	0.97

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

LitVar

Other links and lift over

dbSNP: rs12089381; hg19: chr1-204091014; COSMIC: COSV65827496; COSMIC: COSV65827496;