12-24339559-A-G

Variant names:

• chr12-24339559-A-G
• rs574115
• NM_152989.5:c.-99+29004T>C

Variant summary

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

The NM_152989.5(SOX5):​c.-99+29004T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.712 in 152,100 control chromosomes in the GnomAD database, including 38,757 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 0.71 (38757 hom., cov: 32)
• Consequence: SOX5 NM_152989.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.402

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=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.834 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SOX5	NM_152989.5	c.-99+29004T>C		intron_variant	Intron 3 of 17		NP_694534.1
SOX5	NM_001261414.3	c.-174+29004T>C		intron_variant	Intron 3 of 16		NP_001248343.1
SOX5	XM_011520835.3	c.-99+29004T>C		intron_variant	Intron 3 of 17		XP_011519137.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SOX5	ENST00000646273.1	c.-174+29004T>C		intron_variant	Intron 3 of 16			ENSP00000493866.1
SOX5	ENST00000704300.1	c.-99+29004T>C		intron_variant	Intron 3 of 7			ENSP00000515824.1
SOX5	ENST00000536729.2	c.-174+17779T>C		intron_variant	Intron 1 of 4	5		ENSP00000496161.1

Frequencies

GnomAD3 genomes AF: 0.712 AC: 108230 AN: 151980 Hom.: 38708 Cov.: 32

Gnomad AFR AF: 0.677

Gnomad AMI AF: 0.878

Gnomad AMR AF: 0.796

Gnomad ASJ AF: 0.748

Gnomad EAS AF: 0.855

Gnomad SAS AF: 0.765

Gnomad FIN AF: 0.756

Gnomad MID AF: 0.718

Gnomad NFE AF: 0.689

Gnomad OTH AF: 0.711

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

GnomAD4 genome AF: 0.712 AC: 108345 AN: 152100 Hom.: 38757 Cov.: 32 AF XY: 0.719 AC XY: 53488 AN XY: 74350

Gnomad4 AFR AF: 0.677

Gnomad4 AMR AF: 0.796

Gnomad4 ASJ AF: 0.748

Gnomad4 EAS AF: 0.855

Gnomad4 SAS AF: 0.767

Gnomad4 FIN AF: 0.756

Gnomad4 NFE AF: 0.689

Gnomad4 OTH AF: 0.714

Alfa AF: 0.664 Hom.: 5183

Bravo AF: 0.717

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.2
DANN	Benign	0.42

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs574115; hg19: chr12-24492493;