12-24405386-C-T

Position:

• chr12-24405386-C-T

Variant summary

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

The NM_152989.5(SOX5):​c.-176+2099G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.395 in 151,880 control chromosomes in the GnomAD database, including 12,275 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 0.39 (12275 hom., cov: 31)
• Consequence: SOX5 NM_152989.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.887

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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.555 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SOX5	NM_001261414.3	c.-251+2099G>A		intron_variant			NP_001248343.1
SOX5	NM_152989.5	c.-176+2099G>A		intron_variant			NP_694534.1
SOX5	XM_011520835.3	c.-176+2099G>A		intron_variant			XP_011519137.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SOX5	ENST00000446891.7	c.-250-36747G>A		intron_variant		5		ENSP00000494627
SOX5	ENST00000646273.1	c.-251+2099G>A		intron_variant				ENSP00000493866
SOX5	ENST00000704300.1	c.-176+2099G>A		intron_variant				ENSP00000515824

Frequencies

GnomAD3 genomes AF: 0.395 AC: 59879 AN: 151762 Hom.: 12259 Cov.: 31

Gnomad AFR AF: 0.348

Gnomad AMI AF: 0.527

Gnomad AMR AF: 0.504

Gnomad ASJ AF: 0.365

Gnomad EAS AF: 0.573

Gnomad SAS AF: 0.452

Gnomad FIN AF: 0.374

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.384

Gnomad OTH AF: 0.378

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

GnomAD4 genome AF: 0.395 AC: 59944 AN: 151880 Hom.: 12275 Cov.: 31 AF XY: 0.402 AC XY: 29823 AN XY: 74222

Gnomad4 AFR AF: 0.348

Gnomad4 AMR AF: 0.505

Gnomad4 ASJ AF: 0.365

Gnomad4 EAS AF: 0.573

Gnomad4 SAS AF: 0.452

Gnomad4 FIN AF: 0.374

Gnomad4 NFE AF: 0.385

Gnomad4 OTH AF: 0.380

Alfa AF: 0.385 Hom.: 18354

Bravo AF: 0.403

Asia WGS AF: 0.492 AC: 1711 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.94
DANN	Benign	0.64

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1396208; hg19: chr12-24558320;