rs10766295

Variant names:

• chr11-16083844-T-C
• rs10766295
• NM_001367873.1:c.1101+12152A>G

Your query was ambiguous. Multiple possible variants found:

• chr11-16083844-T-C
• chr11-16083844-T-G

Variant summary

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

The NM_001367873.1(SOX6):​c.1101+12152A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.31 in 152,052 control chromosomes in the GnomAD database, including 8,775 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 0.31 (8775 hom., cov: 32)
• Consequence: SOX6 NM_001367873.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.485
• Publications: 3 publications found

Genes affected

SOX6 (HGNC:16421): (SRY-box transcription factor 6) This gene encodes a member of the D subfamily of sex determining region y-related transcription factors that are characterized by a conserved DNA-binding domain termed the high mobility group box and by their ability to bind the minor groove of DNA. The encoded protein is a transcriptional activator that is required for normal development of the central nervous system, chondrogenesis and maintenance of cardiac and skeletal muscle cells. The encoded protein interacts with other family members to cooperatively activate gene expression. Alternative splicing results in multiple transcript variants.[provided by RefSeq, Mar 2009]

SOX6 Gene-Disease associations (from GenCC):

• Tolchin-Le Caignec syndrome

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, PanelApp Australia, G2P, Illumina

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.41 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SOX6	NM_001367873.1	c.1101+12152A>G		intron_variant	Intron 9 of 15	ENST00000683767.1	NP_001354802.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SOX6	ENST00000683767.1	c.1101+12152A>G		intron_variant	Intron 9 of 15		NM_001367873.1	ENSP00000507545.1

Frequencies

GnomAD3 genomes AF: 0.310 AC: 47062 AN: 151934 Hom.: 8776 Cov.: 32

Gnomad AFR AF: 0.0985

Gnomad AMI AF: 0.411

Gnomad AMR AF: 0.393

Gnomad ASJ AF: 0.258

Gnomad EAS AF: 0.238

Gnomad SAS AF: 0.306

Gnomad FIN AF: 0.395

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.414

Gnomad OTH AF: 0.298

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

GnomAD4 genome AF: 0.310 AC: 47069 AN: 152052 Hom.: 8775 Cov.: 32 AF XY: 0.309 AC XY: 22983 AN XY: 74336

African (AFR) AF: 0.0983 AC: 4080 AN: 41524

American (AMR) AF: 0.394 AC: 6007 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.258 AC: 893 AN: 3466

East Asian (EAS) AF: 0.238 AC: 1232 AN: 5172

South Asian (SAS) AF: 0.306 AC: 1476 AN: 4826

European-Finnish (FIN) AF: 0.395 AC: 4174 AN: 10572

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.414 AC: 28150 AN: 67924

Other (OTH) AF: 0.293 AC: 617 AN: 2106

Alfa AF: 0.370 Hom.: 33866

Bravo AF: 0.298

Asia WGS AF: 0.236 AC: 822 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	7.6
DANN	Benign	0.81
PhyloP100		0.48
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: rs10766295; hg19: chr11-16105390;