12-24125887-C-G

Variant names:

• chr12-24125887-C-G
• rs7979575
• NM_152989.5:c.-2+151329G>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.-2+151329G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.782 in 152,072 control chromosomes in the GnomAD database, including 46,826 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 0.78 (46826 hom., cov: 31)
• Consequence: SOX5 NM_152989.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.05
• Publications: 6 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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.821 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.-2+151329G>C		intron	N/A	NP_694534.1
	SOX5	NM_001261414.3		c.-2+87456G>C		intron	N/A	NP_001248343.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SOX5	ENST00000646273.1		c.-2+87456G>C		intron	N/A	ENSP00000493866.1
	SOX5	ENST00000704300.1		c.-2+151329G>C		intron	N/A	ENSP00000515824.1
	SOX5	ENST00000536729.2	TSL:5	c.-2+87456G>C		intron	N/A	ENSP00000496161.1

Frequencies

GnomAD3 genomes AF: 0.782 AC: 118824 AN: 151952 Hom.: 46769 Cov.: 31

Gnomad AFR AF: 0.698

Gnomad AMI AF: 0.936

Gnomad AMR AF: 0.818

Gnomad ASJ AF: 0.719

Gnomad EAS AF: 0.737

Gnomad SAS AF: 0.761

Gnomad FIN AF: 0.813

Gnomad MID AF: 0.694

Gnomad NFE AF: 0.827

Gnomad OTH AF: 0.783

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

GnomAD4 genome AF: 0.782 AC: 118939 AN: 152072 Hom.: 46826 Cov.: 31 AF XY: 0.781 AC XY: 58101 AN XY: 74350

African (AFR) AF: 0.699 AC: 28963 AN: 41456

American (AMR) AF: 0.818 AC: 12507 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.719 AC: 2494 AN: 3470

East Asian (EAS) AF: 0.738 AC: 3805 AN: 5158

South Asian (SAS) AF: 0.760 AC: 3660 AN: 4818

European-Finnish (FIN) AF: 0.813 AC: 8598 AN: 10578

Middle Eastern (MID) AF: 0.688 AC: 201 AN: 292

European-Non Finnish (NFE) AF: 0.827 AC: 56197 AN: 67990

Other (OTH) AF: 0.785 AC: 1660 AN: 2114

Alfa AF: 0.809 Hom.: 24076

Bravo AF: 0.779

Asia WGS AF: 0.766 AC: 2665 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.071
DANN	Benign	0.34
PhyloP100		-1.1

Splicing

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

Other links and lift over

dbSNP: rs7979575; hg19: chr12-24278821;