11-16258758-A-T

Variant names:

• chr11-16258758-A-T
• rs10832576
• NM_001367873.1:c.446-24087T>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.446-24087T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.782 in 151,558 control chromosomes in the GnomAD database, including 46,501 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 0.78 (46501 hom., cov: 29)
• Consequence: SOX6 NM_001367873.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.768
• 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):

• 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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.796 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.446-24087T>A		intron	N/A	NP_001354802.1
	SOX6	NM_001145819.2		c.446-24087T>A		intron	N/A	NP_001139291.2
	SOX6	NM_033326.3		c.446-24087T>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.446-24087T>A		intron	N/A	ENSP00000507545.1
	SOX6	ENST00000528429.5	TSL:1	c.446-24087T>A		intron	N/A	ENSP00000433233.1
	SOX6	ENST00000396356.7	TSL:1	c.446-24087T>A		intron	N/A	ENSP00000379644.3

Frequencies

GnomAD3 genomes AF: 0.782 AC: 118470 AN: 151440 Hom.: 46474 Cov.: 29

Gnomad AFR AF: 0.763

Gnomad AMI AF: 0.782

Gnomad AMR AF: 0.690

Gnomad ASJ AF: 0.842

Gnomad EAS AF: 0.752

Gnomad SAS AF: 0.765

Gnomad FIN AF: 0.866

Gnomad MID AF: 0.794

Gnomad NFE AF: 0.802

Gnomad OTH AF: 0.795

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

GnomAD4 genome AF: 0.782 AC: 118547 AN: 151558 Hom.: 46501 Cov.: 29 AF XY: 0.784 AC XY: 58054 AN XY: 74056

African (AFR) AF: 0.763 AC: 31530 AN: 41348

American (AMR) AF: 0.689 AC: 10467 AN: 15182

Ashkenazi Jewish (ASJ) AF: 0.842 AC: 2923 AN: 3470

East Asian (EAS) AF: 0.753 AC: 3877 AN: 5152

South Asian (SAS) AF: 0.766 AC: 3679 AN: 4802

European-Finnish (FIN) AF: 0.866 AC: 9119 AN: 10524

Middle Eastern (MID) AF: 0.796 AC: 234 AN: 294

European-Non Finnish (NFE) AF: 0.802 AC: 54326 AN: 67772

Other (OTH) AF: 0.798 AC: 1680 AN: 2104

Alfa AF: 0.802 Hom.: 6087

Bravo AF: 0.768

Asia WGS AF: 0.805 AC: 2795 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	8.7
DANN	Benign	0.89
PhyloP100		0.77
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: rs10832576; hg19: chr11-16280304;