12-24405386-C-T

Variant names:

• chr12-24405386-C-T
• rs1396208
• NM_152989.5:c.-176+2099G>A

Variant summary

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

The NM_152989.5(SOX5):​c.-176+2099G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.395 in 151,880 control chromosomes in the GnomAD database, including 12,275 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 0.39 (12275 hom., cov: 31)
• Consequence: SOX5 NM_152989.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.887
• Publications: 5 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.555 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.-176+2099G>A		intron	N/A	NP_694534.1	T2CYZ2
	SOX5	NM_001261414.3		c.-251+2099G>A		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.-251+2099G>A		intron	N/A	ENSP00000493866.1	P35711-4
	SOX5	ENST00000704300.1		c.-176+2099G>A		intron	N/A	ENSP00000515824.1	A0A994J4I4
	SOX5	ENST00000446891.7	TSL:5	c.-250-36747G>A		intron	N/A	ENSP00000494627.1	A0A2R8Y5Q1

Frequencies

GnomAD3 genomes AF: 0.395 AC: 59879 AN: 151762 Hom.: 12259 Cov.: 31

Gnomad AFR AF: 0.348

Gnomad AMI AF: 0.527

Gnomad AMR AF: 0.504

Gnomad ASJ AF: 0.365

Gnomad EAS AF: 0.573

Gnomad SAS AF: 0.452

Gnomad FIN AF: 0.374

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.384

Gnomad OTH AF: 0.378

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

GnomAD4 genome AF: 0.395 AC: 59944 AN: 151880 Hom.: 12275 Cov.: 31 AF XY: 0.402 AC XY: 29823 AN XY: 74222

African (AFR) AF: 0.348 AC: 14402 AN: 41394

American (AMR) AF: 0.505 AC: 7709 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.365 AC: 1268 AN: 3472

East Asian (EAS) AF: 0.573 AC: 2961 AN: 5172

South Asian (SAS) AF: 0.452 AC: 2163 AN: 4784

European-Finnish (FIN) AF: 0.374 AC: 3942 AN: 10530

Middle Eastern (MID) AF: 0.313 AC: 92 AN: 294

European-Non Finnish (NFE) AF: 0.385 AC: 26127 AN: 67946

Other (OTH) AF: 0.380 AC: 799 AN: 2102

Alfa AF: 0.385 Hom.: 21564

Bravo AF: 0.403

Asia WGS AF: 0.492 AC: 1711 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.94
DANN	Benign	0.64
PhyloP100		-0.89

Splicing

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

Other links and lift over

dbSNP: rs1396208; hg19: chr12-24558320;