rs11046992

Positions:

• chr12-23584632-G-A
• chr12-23584632-G-C
• chr12-23584632-G-T

Variant summary

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

The NM_006940.6(SOX5):​c.1165-8794C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.28 in 1,558,052 control chromosomes in the GnomAD database, including 63,769 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 0.24 (4881 hom., cov: 32)
  • Exomes 𝑓: 0.28 (58888 hom.)
• Consequence: SOX5 NM_006940.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.800

Genes affected

SOX5 (HGNC:11201): (SRY-box transcription factor 5) 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 the cell fate. The encoded protein may act as a transcriptional regulator after forming a protein complex with other proteins. The encoded protein may play a role in chondrogenesis. A pseudogene of this gene is located on chromosome 8. Multiple transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.301 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SOX5	NM_006940.6	c.1165-8794C>T		intron_variant		ENST00000451604.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SOX5	ENST00000451604.7	c.1165-8794C>T		intron_variant		1	NM_006940.6	A1

Frequencies

GnomAD3 genomes AF: 0.236 AC: 35776 AN: 151862 Hom.: 4880 Cov.: 32

Gnomad AFR AF: 0.101

Gnomad AMI AF: 0.490

Gnomad AMR AF: 0.188

Gnomad ASJ AF: 0.394

Gnomad EAS AF: 0.314

Gnomad SAS AF: 0.281

Gnomad FIN AF: 0.342

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.290

Gnomad OTH AF: 0.247

GnomAD4 exome AF: 0.285 AC: 400552 AN: 1406072 Hom.: 58888 Cov.: 24 AF XY: 0.286 AC XY: 200956 AN XY: 702616

Gnomad4 AFR exome AF: 0.0940

Gnomad4 AMR exome AF: 0.141

Gnomad4 ASJ exome AF: 0.394

Gnomad4 EAS exome AF: 0.294

Gnomad4 SAS exome AF: 0.282

Gnomad4 FIN exome AF: 0.329

Gnomad4 NFE exome AF: 0.291

Gnomad4 OTH exome AF: 0.295

GnomAD4 genome AF: 0.236 AC: 35799 AN: 151980 Hom.: 4881 Cov.: 32 AF XY: 0.238 AC XY: 17711 AN XY: 74286

Gnomad4 AFR AF: 0.101

Gnomad4 AMR AF: 0.188

Gnomad4 ASJ AF: 0.394

Gnomad4 EAS AF: 0.314

Gnomad4 SAS AF: 0.281

Gnomad4 FIN AF: 0.342

Gnomad4 NFE AF: 0.291

Gnomad4 OTH AF: 0.252

Alfa AF: 0.275 Hom.: 10237

Bravo AF: 0.217

Asia WGS AF: 0.276 AC: 963 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.5
DANN	Benign	0.42

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: rs11046992; hg19: chr12-23737566; COSMIC: COSV58630620; COSMIC: COSV58630620;