12-24339559-A-G

Variant names:

• chr12-24339559-A-G
• rs574115
• NM_152989.5:c.-99+29004T>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+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
• 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: Labcorp Genetics (formerly Invitae), G2P, ClinGen
• 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=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.834 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SOX5	NM_152989.5		c.-99+29004T>C		intron	N/A	NP_694534.1
	SOX5	NM_001261414.3		c.-174+29004T>C		intron	N/A	NP_001248343.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SOX5	ENST00000646273.1		c.-174+29004T>C		intron	N/A	ENSP00000493866.1
	SOX5	ENST00000704300.1		c.-99+29004T>C		intron	N/A	ENSP00000515824.1
	SOX5	ENST00000536729.2	TSL:5	c.-174+17779T>C		intron	N/A	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

African (AFR) AF: 0.677 AC: 28095 AN: 41474

American (AMR) AF: 0.796 AC: 12183 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.748 AC: 2592 AN: 3466

East Asian (EAS) AF: 0.855 AC: 4420 AN: 5172

South Asian (SAS) AF: 0.767 AC: 3699 AN: 4822

European-Finnish (FIN) AF: 0.756 AC: 7997 AN: 10572

Middle Eastern (MID) AF: 0.711 AC: 209 AN: 294

European-Non Finnish (NFE) AF: 0.689 AC: 46842 AN: 67982

Other (OTH) AF: 0.714 AC: 1507 AN: 2110

Alfa AF: 0.664 Hom.: 5183

Bravo AF: 0.717

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.2
DANN	Benign	0.42
PhyloP100		-0.40

Splicing

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

Other links and lift over

dbSNP: rs574115; hg19: chr12-24492493;