rs11023907

Variant names:

• chr11-16302903-G-T
• rs11023907
• NM_001367873.1:c.445+15543C>A

Variant summary

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

The NM_001367873.1(SOX6):​c.445+15543C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.169 in 151,898 control chromosomes in the GnomAD database, including 2,639 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 0.17 (2639 hom., cov: 30)
• Consequence: SOX6 NM_001367873.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.714
• Publications: 5 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):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• Tolchin-Le Caignec syndrome

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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.283 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001367873.1. 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
	SOX6	NM_001367873.1	MANE Select	c.445+15543C>A		intron	N/A	NP_001354802.1	P35712-1
	SOX6	NM_001145819.2		c.445+15543C>A		intron	N/A	NP_001139291.2	P35712-1
	SOX6	NM_033326.3		c.445+15543C>A		intron	N/A	NP_201583.2	P35712-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SOX6	ENST00000683767.1	MANE Select	c.445+15543C>A		intron	N/A	ENSP00000507545.1	P35712-1
	SOX6	ENST00000528429.5	TSL:1	c.445+15543C>A		intron	N/A	ENSP00000433233.1	P35712-1
	SOX6	ENST00000396356.7	TSL:1	c.445+15543C>A		intron	N/A	ENSP00000379644.3	P35712-3

Frequencies

GnomAD3 genomes AF: 0.169 AC: 25632 AN: 151782 Hom.: 2634 Cov.: 30

Gnomad AFR AF: 0.0624

Gnomad AMI AF: 0.218

Gnomad AMR AF: 0.289

Gnomad ASJ AF: 0.181

Gnomad EAS AF: 0.241

Gnomad SAS AF: 0.236

Gnomad FIN AF: 0.133

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.200

Gnomad OTH AF: 0.175

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

GnomAD4 genome AF: 0.169 AC: 25645 AN: 151898 Hom.: 2639 Cov.: 30 AF XY: 0.169 AC XY: 12561 AN XY: 74208

African (AFR) AF: 0.0626 AC: 2594 AN: 41466

American (AMR) AF: 0.290 AC: 4418 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.181 AC: 627 AN: 3468

East Asian (EAS) AF: 0.241 AC: 1235 AN: 5126

South Asian (SAS) AF: 0.235 AC: 1133 AN: 4822

European-Finnish (FIN) AF: 0.133 AC: 1396 AN: 10520

Middle Eastern (MID) AF: 0.211 AC: 62 AN: 294

European-Non Finnish (NFE) AF: 0.200 AC: 13619 AN: 67936

Other (OTH) AF: 0.172 AC: 362 AN: 2104

Alfa AF: 0.183 Hom.: 505

Bravo AF: 0.176

Asia WGS AF: 0.184 AC: 642 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.28
DANN	Benign	0.74
PhyloP100		-0.71
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: rs11023907; hg19: chr11-16324449;