11-16256807-G-C

Variant names:

• chr11-16256807-G-C
• rs12798980
• NM_001367873.1:c.446-22136C>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.446-22136C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.166 in 151,736 control chromosomes in the GnomAD database, including 2,591 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 (2591 hom., cov: 32)
• Consequence: SOX6 NM_001367873.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.779
• Publications: 4 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: G2P, Illumina, Ambry Genetics, PanelApp Australia, Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.282 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.446-22136C>G		intron	N/A	NP_001354802.1	P35712-1
	SOX6	NM_001145819.2		c.446-22136C>G		intron	N/A	NP_001139291.2	P35712-1
	SOX6	NM_033326.3		c.446-22136C>G		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.446-22136C>G		intron	N/A	ENSP00000507545.1	P35712-1
	SOX6	ENST00000528429.5	TSL:1	c.446-22136C>G		intron	N/A	ENSP00000433233.1	P35712-1
	SOX6	ENST00000396356.7	TSL:1	c.446-22136C>G		intron	N/A	ENSP00000379644.3	P35712-3

Frequencies

GnomAD3 genomes AF: 0.166 AC: 25233 AN: 151618 Hom.: 2587 Cov.: 32

Gnomad AFR AF: 0.0600

Gnomad AMI AF: 0.216

Gnomad AMR AF: 0.288

Gnomad ASJ AF: 0.158

Gnomad EAS AF: 0.249

Gnomad SAS AF: 0.234

Gnomad FIN AF: 0.134

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.198

Gnomad OTH AF: 0.170

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

GnomAD4 genome AF: 0.166 AC: 25236 AN: 151736 Hom.: 2591 Cov.: 32 AF XY: 0.167 AC XY: 12399 AN XY: 74178

African (AFR) AF: 0.0599 AC: 2485 AN: 41498

American (AMR) AF: 0.289 AC: 4398 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.158 AC: 545 AN: 3458

East Asian (EAS) AF: 0.249 AC: 1286 AN: 5172

South Asian (SAS) AF: 0.233 AC: 1125 AN: 4818

European-Finnish (FIN) AF: 0.134 AC: 1415 AN: 10564

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

European-Non Finnish (NFE) AF: 0.198 AC: 13377 AN: 67680

Other (OTH) AF: 0.167 AC: 352 AN: 2110

Alfa AF: 0.0775 Hom.: 103

Bravo AF: 0.173

Asia WGS AF: 0.182 AC: 631 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.52
DANN	Benign	0.42
PhyloP100		-0.78
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs12798980;

hg19: chr11-16278353;

COSMIC: COSV57053281;

COSMIC: COSV57053281;