chr11-16228637-C-T

Variant names:

• chr11-16228637-C-T
• rs1401454
• NM_001367873.1:c.535+5945G>A

Variant summary

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

The NM_001145819.2(SOX6):​c.535+5945G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.428 in 151,882 control chromosomes in the GnomAD database, including 14,216 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 0.43 (14216 hom., cov: 31)
• Consequence: SOX6 NM_001145819.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.987
• Publications: 15 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=-0.99).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.579 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001145819.2. 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.535+5945G>A		intron	N/A	NP_001354802.1
	SOX6	NM_001145819.2		c.535+5945G>A		intron	N/A	NP_001139291.2
	SOX6	NM_033326.3		c.535+5945G>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.535+5945G>A		intron	N/A	ENSP00000507545.1
	SOX6	ENST00000528429.5	TSL:1	c.535+5945G>A		intron	N/A	ENSP00000433233.1
	SOX6	ENST00000396356.7	TSL:1	c.535+5945G>A		intron	N/A	ENSP00000379644.3

Frequencies

GnomAD3 genomes AF: 0.428 AC: 64978 AN: 151764 Hom.: 14206 Cov.: 31

Gnomad AFR AF: 0.455

Gnomad AMI AF: 0.325

Gnomad AMR AF: 0.496

Gnomad ASJ AF: 0.431

Gnomad EAS AF: 0.495

Gnomad SAS AF: 0.596

Gnomad FIN AF: 0.313

Gnomad MID AF: 0.453

Gnomad NFE AF: 0.399

Gnomad OTH AF: 0.411

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

GnomAD4 genome AF: 0.428 AC: 65035 AN: 151882 Hom.: 14216 Cov.: 31 AF XY: 0.430 AC XY: 31901 AN XY: 74226

African (AFR) AF: 0.455 AC: 18852 AN: 41426

American (AMR) AF: 0.496 AC: 7556 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.431 AC: 1493 AN: 3468

East Asian (EAS) AF: 0.495 AC: 2556 AN: 5166

South Asian (SAS) AF: 0.597 AC: 2875 AN: 4818

European-Finnish (FIN) AF: 0.313 AC: 3304 AN: 10540

Middle Eastern (MID) AF: 0.446 AC: 131 AN: 294

European-Non Finnish (NFE) AF: 0.399 AC: 27109 AN: 67916

Other (OTH) AF: 0.409 AC: 863 AN: 2108

Alfa AF: 0.410 Hom.: 26777

Bravo AF: 0.439

Asia WGS AF: 0.499 AC: 1735 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.41
DANN	Benign	0.26
PhyloP100		-0.99
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: rs1401454; hg19: chr11-16250183;