12-23700135-T-C

Position:

• chr12-23700135-T-C

Variant summary

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

The NM_006940.6(SOX5):​c.810+34549A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.401 in 151,968 control chromosomes in the GnomAD database, including 12,937 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 0.40 (12937 hom., cov: 32)
• Consequence: SOX5 NM_006940.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.100

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.547 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SOX5	NM_006940.6	c.810+34549A>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.810+34549A>G		intron_variant		1	NM_006940.6	ENSP00000398273	A1

Frequencies

GnomAD3 genomes AF: 0.401 AC: 60926 AN: 151848 Hom.: 12920 Cov.: 32

Gnomad AFR AF: 0.553

Gnomad AMI AF: 0.427

Gnomad AMR AF: 0.295

Gnomad ASJ AF: 0.330

Gnomad EAS AF: 0.230

Gnomad SAS AF: 0.269

Gnomad FIN AF: 0.427

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.355

Gnomad OTH AF: 0.383

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

GnomAD4 genome AF: 0.401 AC: 60983 AN: 151968 Hom.: 12937 Cov.: 32 AF XY: 0.398 AC XY: 29602 AN XY: 74284

Gnomad4 AFR AF: 0.553

Gnomad4 AMR AF: 0.295

Gnomad4 ASJ AF: 0.330

Gnomad4 EAS AF: 0.229

Gnomad4 SAS AF: 0.269

Gnomad4 FIN AF: 0.427

Gnomad4 NFE AF: 0.355

Gnomad4 OTH AF: 0.380

Alfa AF: 0.347 Hom.: 19231

Bravo AF: 0.397

Asia WGS AF: 0.255 AC: 889 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.5
DANN	Benign	0.72

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: rs725124; hg19: chr12-23853069;