rs10771006

Variant names:

• chr12-23601275-T-C
• rs10771006
• NM_006940.6:c.1164+3112A>G

Variant summary

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

The NM_006940.6(SOX5):​c.1164+3112A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.238 in 151,980 control chromosomes in the GnomAD database, including 5,258 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 0.24 (5258 hom., cov: 30)
• Consequence: SOX5 NM_006940.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.84
• Publications: 4 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=-0.49).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.39 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006940.6. 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_006940.6	MANE Select	c.1164+3112A>G		intron	N/A	NP_008871.3
	SOX5	NM_001261415.3		c.1134+3112A>G		intron	N/A	NP_001248344.1	P35711-5
	SOX5	NM_152989.5		c.1125+3112A>G		intron	N/A	NP_694534.1	T2CYZ2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SOX5	ENST00000451604.7	TSL:1 MANE Select	c.1164+3112A>G		intron	N/A	ENSP00000398273.2	P35711-1
	SOX5	ENST00000900854.1		c.1164+3112A>G		intron	N/A	ENSP00000570913.1
	SOX5	ENST00000900855.1		c.1164+3112A>G		intron	N/A	ENSP00000570914.1

Frequencies

GnomAD3 genomes AF: 0.238 AC: 36070 AN: 151860 Hom.: 5253 Cov.: 30

Gnomad AFR AF: 0.395

Gnomad AMI AF: 0.0725

Gnomad AMR AF: 0.284

Gnomad ASJ AF: 0.158

Gnomad EAS AF: 0.228

Gnomad SAS AF: 0.0893

Gnomad FIN AF: 0.165

Gnomad MID AF: 0.204

Gnomad NFE AF: 0.161

Gnomad OTH AF: 0.224

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

GnomAD4 genome AF: 0.238 AC: 36107 AN: 151980 Hom.: 5258 Cov.: 30 AF XY: 0.234 AC XY: 17360 AN XY: 74286

African (AFR) AF: 0.395 AC: 16370 AN: 41404

American (AMR) AF: 0.285 AC: 4343 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.158 AC: 548 AN: 3472

East Asian (EAS) AF: 0.228 AC: 1177 AN: 5156

South Asian (SAS) AF: 0.0877 AC: 422 AN: 4812

European-Finnish (FIN) AF: 0.165 AC: 1743 AN: 10584

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.161 AC: 10914 AN: 67984

Other (OTH) AF: 0.222 AC: 467 AN: 2104

Alfa AF: 0.191 Hom.: 12177

Bravo AF: 0.262

Asia WGS AF: 0.168 AC: 583 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	21
DANN	Benign	0.84
PhyloP100		2.8
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs10771006; hg19: chr12-23754209;