11-16008821-G-T

Variant names:

• chr11-16008821-G-T
• rs7947008
• NM_001367873.1:c.1732+6121C>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001367873.1(SOX6):​c.1732+6121C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0878 in 152,064 control chromosomes in the GnomAD database, including 1,208 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 0.088 (1208 hom., cov: 32)
• Consequence: SOX6 NM_001367873.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.22
• Publications: 2 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.33).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.343 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SOX6	NM_001367873.1	MANE Select	c.1732+6121C>A		intron	N/A	NP_001354802.1
	SOX6	NM_001145819.2		c.1732+6121C>A		intron	N/A	NP_001139291.2
	SOX6	NM_033326.3		c.1732+6121C>A		intron	N/A	NP_201583.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SOX6	ENST00000683767.1	MANE Select	c.1732+6121C>A		intron	N/A	ENSP00000507545.1
	SOX6	ENST00000528429.5	TSL:1	c.1732+6121C>A		intron	N/A	ENSP00000433233.1
	SOX6	ENST00000396356.7	TSL:1	c.1732+6121C>A		intron	N/A	ENSP00000379644.3

Frequencies

GnomAD3 genomes AF: 0.0877 AC: 13328 AN: 151944 Hom.: 1203 Cov.: 32

Gnomad AFR AF: 0.182

Gnomad AMI AF: 0.0252

Gnomad AMR AF: 0.122

Gnomad ASJ AF: 0.0559

Gnomad EAS AF: 0.357

Gnomad SAS AF: 0.0459

Gnomad FIN AF: 0.0849

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.00916

Gnomad OTH AF: 0.0699

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

GnomAD4 genome AF: 0.0878 AC: 13351 AN: 152064 Hom.: 1208 Cov.: 32 AF XY: 0.0920 AC XY: 6837 AN XY: 74332

African (AFR) AF: 0.182 AC: 7550 AN: 41490

American (AMR) AF: 0.122 AC: 1859 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.0559 AC: 194 AN: 3470

East Asian (EAS) AF: 0.356 AC: 1830 AN: 5134

South Asian (SAS) AF: 0.0449 AC: 217 AN: 4828

European-Finnish (FIN) AF: 0.0849 AC: 898 AN: 10582

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.00916 AC: 623 AN: 67976

Other (OTH) AF: 0.0696 AC: 147 AN: 2112

Alfa AF: 0.0408 Hom.: 2107

Bravo AF: 0.102

Asia WGS AF: 0.204 AC: 706 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.33
CADD	Benign	20
DANN	Benign	0.80
PhyloP100		1.2
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: rs7947008; hg19: chr11-16030367; COSMIC: COSV57049918;