chr12-24241438-T-C

Variant names:

• chr12-24241438-T-C
• rs1522232
• NM_152989.5:c.-2+35778A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_152989.5(SOX5):​c.-2+35778A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.468 in 151,950 control chromosomes in the GnomAD database, including 17,206 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 0.47 (17206 hom., cov: 32)
• Consequence: SOX5 NM_152989.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0560
• Publications: 14 publications found

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-AS1 (HGNC:53311): (SOX5 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.516 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SOX5	NM_152989.5	c.-2+35778A>G		intron_variant	Intron 4 of 17		NP_694534.1
SOX5	NM_001261414.3	c.-76-28021A>G		intron_variant	Intron 4 of 16		NP_001248343.1
SOX5	XM_011520835.3	c.-2+35778A>G		intron_variant	Intron 4 of 17		XP_011519137.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SOX5	ENST00000646273.1	c.-76-28021A>G		intron_variant	Intron 4 of 16			ENSP00000493866.1
SOX5	ENST00000704300.1	c.-2+35778A>G		intron_variant	Intron 4 of 7			ENSP00000515824.1
SOX5	ENST00000536729.2	c.-76-28021A>G		intron_variant	Intron 2 of 4	5		ENSP00000496161.1

Frequencies

GnomAD3 genomes AF: 0.468 AC: 71077 AN: 151832 Hom.: 17197 Cov.: 32

Gnomad AFR AF: 0.394

Gnomad AMI AF: 0.457

Gnomad AMR AF: 0.455

Gnomad ASJ AF: 0.489

Gnomad EAS AF: 0.226

Gnomad SAS AF: 0.353

Gnomad FIN AF: 0.610

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.521

Gnomad OTH AF: 0.453

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

GnomAD4 genome AF: 0.468 AC: 71111 AN: 151950 Hom.: 17206 Cov.: 32 AF XY: 0.468 AC XY: 34761 AN XY: 74238

African (AFR) AF: 0.394 AC: 16326 AN: 41446

American (AMR) AF: 0.456 AC: 6951 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.489 AC: 1696 AN: 3470

East Asian (EAS) AF: 0.225 AC: 1163 AN: 5172

South Asian (SAS) AF: 0.352 AC: 1696 AN: 4814

European-Finnish (FIN) AF: 0.610 AC: 6438 AN: 10548

Middle Eastern (MID) AF: 0.405 AC: 119 AN: 294

European-Non Finnish (NFE) AF: 0.521 AC: 35364 AN: 67930

Other (OTH) AF: 0.447 AC: 941 AN: 2104

Alfa AF: 0.500 Hom.: 80618

Bravo AF: 0.454

Asia WGS AF: 0.275 AC: 957 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.2
DANN	Benign	0.86
PhyloP100		-0.056

Splicing

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

Other links and lift over

dbSNP: rs1522232; hg19: chr12-24394372;