12-24012537-T-C

Position:

• chr12-24012537-T-C

Variant summary

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

The NM_152989.5(SOX5):​c.-1-116513A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.797 in 152,098 control chromosomes in the GnomAD database, including 48,494 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 0.80 (48494 hom., cov: 32)
• Consequence: SOX5 NM_152989.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0100

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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.91 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SOX5	NM_001261414.3	c.-1-116513A>G		intron_variant
SOX5	NM_152989.5	c.-1-116513A>G		intron_variant
SOX5	XM_011520835.3	c.-1-116513A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SOX5	ENST00000446891.7	c.-1-116513A>G		intron_variant		5
SOX5	ENST00000536729.2	c.-1-116513A>G		intron_variant		5
SOX5	ENST00000646273.1	c.-1-116513A>G		intron_variant

Frequencies

GnomAD3 genomes AF: 0.797 AC: 121137 AN: 151980 Hom.: 48457 Cov.: 32

Gnomad AFR AF: 0.722

Gnomad AMI AF: 0.792

Gnomad AMR AF: 0.836

Gnomad ASJ AF: 0.895

Gnomad EAS AF: 0.932

Gnomad SAS AF: 0.927

Gnomad FIN AF: 0.803

Gnomad MID AF: 0.854

Gnomad NFE AF: 0.808

Gnomad OTH AF: 0.818

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

GnomAD4 genome AF: 0.797 AC: 121229 AN: 152098 Hom.: 48494 Cov.: 32 AF XY: 0.800 AC XY: 59487 AN XY: 74328

Gnomad4 AFR AF: 0.722

Gnomad4 AMR AF: 0.836

Gnomad4 ASJ AF: 0.895

Gnomad4 EAS AF: 0.931

Gnomad4 SAS AF: 0.927

Gnomad4 FIN AF: 0.803

Gnomad4 NFE AF: 0.808

Gnomad4 OTH AF: 0.819

Alfa AF: 0.773 Hom.: 5542

Bravo AF: 0.799

Asia WGS AF: 0.891 AC: 3101 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.3
DANN	Benign	0.57

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2133345; hg19: chr12-24165471;