12-24348226-A-G

Variant names:

• chr12-24348226-A-G
• rs575608
• NM_152989.5:c.-99+20337T>C

Variant summary

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

The NM_152989.5(SOX5):​c.-99+20337T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.336 in 151,698 control chromosomes in the GnomAD database, including 9,861 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 0.34 (9861 hom., cov: 30)
• Consequence: SOX5 NM_152989.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.55
• Publications: 3 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.763 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.-99+20337T>C		intron	N/A	NP_694534.1	T2CYZ2
	SOX5	NM_001261414.3		c.-174+20337T>C		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.-174+20337T>C		intron	N/A	ENSP00000493866.1	P35711-4
	SOX5	ENST00000704300.1		c.-99+20337T>C		intron	N/A	ENSP00000515824.1	A0A994J4I4
	SOX5	ENST00000536729.2	TSL:5	c.-174+9112T>C		intron	N/A	ENSP00000496161.1	A0A2R8Y7P3

Frequencies

GnomAD3 genomes AF: 0.336 AC: 50959 AN: 151580 Hom.: 9841 Cov.: 30

Gnomad AFR AF: 0.246

Gnomad AMI AF: 0.348

Gnomad AMR AF: 0.509

Gnomad ASJ AF: 0.359

Gnomad EAS AF: 0.784

Gnomad SAS AF: 0.594

Gnomad FIN AF: 0.408

Gnomad MID AF: 0.383

Gnomad NFE AF: 0.287

Gnomad OTH AF: 0.336

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

GnomAD4 genome AF: 0.336 AC: 51029 AN: 151698 Hom.: 9861 Cov.: 30 AF XY: 0.353 AC XY: 26155 AN XY: 74112

African (AFR) AF: 0.247 AC: 10202 AN: 41364

American (AMR) AF: 0.510 AC: 7781 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.359 AC: 1243 AN: 3462

East Asian (EAS) AF: 0.783 AC: 4041 AN: 5160

South Asian (SAS) AF: 0.596 AC: 2861 AN: 4804

European-Finnish (FIN) AF: 0.408 AC: 4254 AN: 10438

Middle Eastern (MID) AF: 0.391 AC: 115 AN: 294

European-Non Finnish (NFE) AF: 0.287 AC: 19501 AN: 67910

Other (OTH) AF: 0.339 AC: 714 AN: 2108

Alfa AF: 0.177 Hom.: 386

Bravo AF: 0.343

Asia WGS AF: 0.655 AC: 2276 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	8.5
DANN	Benign	0.58
PhyloP100		1.6

Splicing

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

Other links and lift over

dbSNP: rs575608; hg19: chr12-24501160;