12-24012537-T-C

Variant names:

• chr12-24012537-T-C
• rs2133345
• NM_152989.5:c.-1-116513A>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.-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
• Publications: 2 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 Gene-Disease associations (from GenCC):

• Lamb-Shaffer syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, PanelApp Australia, ClinGen, Labcorp Genetics (formerly Invitae)
• developmental and speech delay due to SOX5 deficiency

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152989.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SOX5	NM_152989.5		c.-1-116513A>G		intron	N/A	NP_694534.1	T2CYZ2
	SOX5	NM_001261414.3		c.-1-116513A>G		intron	N/A	NP_001248343.1	P35711-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SOX5	ENST00000646273.1		c.-1-116513A>G		intron	N/A	ENSP00000493866.1	P35711-4
	SOX5	ENST00000704300.1		c.-1-116513A>G		intron	N/A	ENSP00000515824.1	A0A994J4I4
	SOX5	ENST00000536729.2	TSL:5	c.-1-116513A>G		intron	N/A	ENSP00000496161.1	A0A2R8Y7P3

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

African (AFR) AF: 0.722 AC: 29956 AN: 41486

American (AMR) AF: 0.836 AC: 12771 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.895 AC: 3104 AN: 3468

East Asian (EAS) AF: 0.931 AC: 4825 AN: 5180

South Asian (SAS) AF: 0.927 AC: 4467 AN: 4820

European-Finnish (FIN) AF: 0.803 AC: 8507 AN: 10594

Middle Eastern (MID) AF: 0.844 AC: 248 AN: 294

European-Non Finnish (NFE) AF: 0.808 AC: 54901 AN: 67962

Other (OTH) AF: 0.819 AC: 1728 AN: 2110

Alfa AF: 0.771 Hom.: 5756

Bravo AF: 0.799

Asia WGS AF: 0.891 AC: 3101 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.3
DANN	Benign	0.57
PhyloP100		0.010

Splicing

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

Other links and lift over

dbSNP: rs2133345; hg19: chr12-24165471;