rs550338

chr12-24359103-G-Achr12-24359103-G-T

Variant summary

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

The NM_152989.5(SOX5):c.-99+9460C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.313 in 152,004 control chromosomes in the GnomAD database, including 8,707 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 0.31 (8707 hom., cov: 32)
• Consequence: SOX5 NM_152989.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.223

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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.766 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SOX5	NM_001261414.3	c.-174+9460C>T		intron_variant
SOX5	NM_152989.5	c.-99+9460C>T		intron_variant
SOX5	XM_011520835.3	c.-99+9460C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SOX5	ENST00000446891.7	c.-174+9460C>T		intron_variant		5
SOX5	ENST00000646273.1	c.-174+9460C>T		intron_variant
SOX5	ENST00000704300.1	c.-99+9460C>T		intron_variant

Frequencies

GnomAD3 genomes AF: 0.312 AC: 47419 AN: 151882 Hom.: 8676 Cov.: 32

Gnomad AFR AF: 0.296

Gnomad AMI AF: 0.341

Gnomad AMR AF: 0.475

Gnomad ASJ AF: 0.273

Gnomad EAS AF: 0.787

Gnomad SAS AF: 0.535

Gnomad FIN AF: 0.339

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.230

Gnomad OTH AF: 0.326

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

GnomAD4 genome AF: 0.313 AC: 47505 AN: 152004 Hom.: 8707 Cov.: 32 AF XY: 0.328 AC XY: 24369 AN XY: 74306

Gnomad4 AFR AF: 0.297

Gnomad4 AMR AF: 0.477

Gnomad4 ASJ AF: 0.273

Gnomad4 EAS AF: 0.786

Gnomad4 SAS AF: 0.535

Gnomad4 FIN AF: 0.339

Gnomad4 NFE AF: 0.230

Gnomad4 OTH AF: 0.328

Alfa AF: 0.255 Hom.: 7515

Bravo AF: 0.324

Asia WGS AF: 0.642 AC: 2233 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	1.7
Dann	Benign	0.32

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs550338; hg19: chr12-24512037;