rs2028162

Variant names:

• chr11-16225929-T-C
• rs2028162
• NM_001367873.1:c.535+8653A>G

Your query was ambiguous. Multiple possible variants found:

• chr11-16225929-T-C
• chr11-16225929-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.535+8653A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.206 in 152,108 control chromosomes in the GnomAD database, including 3,914 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 0.21 (3914 hom., cov: 32)
• Consequence: SOX6 NM_001367873.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.16
• 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=-0.79).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.315 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.535+8653A>G		intron	N/A	NP_001354802.1	P35712-1
	SOX6	NM_001145819.2		c.535+8653A>G		intron	N/A	NP_001139291.2	P35712-1
	SOX6	NM_033326.3		c.535+8653A>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.535+8653A>G		intron	N/A	ENSP00000507545.1	P35712-1
	SOX6	ENST00000528429.5	TSL:1	c.535+8653A>G		intron	N/A	ENSP00000433233.1	P35712-1
	SOX6	ENST00000396356.7	TSL:1	c.535+8653A>G		intron	N/A	ENSP00000379644.3	P35712-3

Frequencies

GnomAD3 genomes AF: 0.206 AC: 31320 AN: 151990 Hom.: 3911 Cov.: 32

Gnomad AFR AF: 0.0706

Gnomad AMI AF: 0.228

Gnomad AMR AF: 0.322

Gnomad ASJ AF: 0.174

Gnomad EAS AF: 0.245

Gnomad SAS AF: 0.237

Gnomad FIN AF: 0.201

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.259

Gnomad OTH AF: 0.208

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

GnomAD4 genome AF: 0.206 AC: 31325 AN: 152108 Hom.: 3914 Cov.: 32 AF XY: 0.206 AC XY: 15329 AN XY: 74348

African (AFR) AF: 0.0705 AC: 2928 AN: 41536

American (AMR) AF: 0.323 AC: 4921 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.174 AC: 604 AN: 3466

East Asian (EAS) AF: 0.245 AC: 1269 AN: 5174

South Asian (SAS) AF: 0.237 AC: 1142 AN: 4826

European-Finnish (FIN) AF: 0.201 AC: 2123 AN: 10570

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.259 AC: 17635 AN: 67964

Other (OTH) AF: 0.204 AC: 431 AN: 2112

Alfa AF: 0.250 Hom.: 2810

Bravo AF: 0.208

Asia WGS AF: 0.190 AC: 662 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	13
DANN	Benign	0.86
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

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

Other links and lift over

dbSNP: rs2028162;

hg19: chr11-16247475;