rs7305773

Positions:

• chr12-23818252-T-C

Variant summary

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

The ENST00000451604.7(SOX5):​c.481+27731A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.115 in 152,198 control chromosomes in the GnomAD database, including 1,139 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 0.11 (1139 hom., cov: 32)
• Consequence: SOX5 ENST00000451604.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.425

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=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.15 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SOX5	NM_006940.6	c.481+27731A>G		intron_variant		ENST00000451604.7	NP_008871.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SOX5	ENST00000451604.7	c.481+27731A>G		intron_variant		1	NM_006940.6	ENSP00000398273	A1

Frequencies

GnomAD3 genomes AF: 0.115 AC: 17444 AN: 152080 Hom.: 1136 Cov.: 32

Gnomad AFR AF: 0.0766

Gnomad AMI AF: 0.133

Gnomad AMR AF: 0.0715

Gnomad ASJ AF: 0.103

Gnomad EAS AF: 0.00193

Gnomad SAS AF: 0.0976

Gnomad FIN AF: 0.152

Gnomad MID AF: 0.118

Gnomad NFE AF: 0.153

Gnomad OTH AF: 0.0976

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.115 AC: 17457 AN: 152198 Hom.: 1139 Cov.: 32 AF XY: 0.115 AC XY: 8523 AN XY: 74386

Gnomad4 AFR AF: 0.0769

Gnomad4 AMR AF: 0.0713

Gnomad4 ASJ AF: 0.103

Gnomad4 EAS AF: 0.00193

Gnomad4 SAS AF: 0.0972

Gnomad4 FIN AF: 0.152

Gnomad4 NFE AF: 0.153

Gnomad4 OTH AF: 0.0966

Alfa AF: 0.142 Hom.: 2135

Bravo AF: 0.106

Asia WGS AF: 0.0430 AC: 152 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.4
DANN	Benign	0.59

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: rs7305773; hg19: chr12-23971186;