12-23729549-G-C

Position:

• chr12-23729549-G-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+5135C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.754 in 152,070 control chromosomes in the GnomAD database, including 43,319 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 0.75 (43319 hom., cov: 33)
• Consequence: SOX5 NM_006940.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.201

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]

SOX5 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.767 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SOX5	NM_006940.6	c.810+5135C>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+5135C>G		intron_variant		1	NM_006940.6	ENSP00000398273.2

Frequencies

GnomAD3 genomes AF: 0.754 AC: 114642 AN: 151952 Hom.: 43293 Cov.: 33

Gnomad AFR AF: 0.737

Gnomad AMI AF: 0.714

Gnomad AMR AF: 0.741

Gnomad ASJ AF: 0.749

Gnomad EAS AF: 0.788

Gnomad SAS AF: 0.720

Gnomad FIN AF: 0.753

Gnomad MID AF: 0.687

Gnomad NFE AF: 0.770

Gnomad OTH AF: 0.726

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

GnomAD4 genome AF: 0.754 AC: 114720 AN: 152070 Hom.: 43319 Cov.: 33 AF XY: 0.752 AC XY: 55884 AN XY: 74350

Gnomad4 AFR AF: 0.737

Gnomad4 AMR AF: 0.741

Gnomad4 ASJ AF: 0.749

Gnomad4 EAS AF: 0.787

Gnomad4 SAS AF: 0.721

Gnomad4 FIN AF: 0.753

Gnomad4 NFE AF: 0.770

Gnomad4 OTH AF: 0.722

Alfa AF: 0.720 Hom.: 2178

Bravo AF: 0.750

Asia WGS AF: 0.746 AC: 2591 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	12
DANN	Benign	0.87

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: rs989278; hg19: chr12-23882483;