chr11-16463754-G-A

Variant names:

• chr11-16463754-G-A
• rs1354329
• ENST00000396356.7:c.-5+12561C>T

Variant summary

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

The NM_033326.3(SOX6):​c.-5+12561C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.287 in 152,090 control chromosomes in the GnomAD database, including 6,457 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 0.29 (6457 hom., cov: 32)
• Consequence: SOX6 NM_033326.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.391
• Publications: 8 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: Illumina, G2P, Labcorp Genetics (formerly Invitae), PanelApp Australia, Ambry Genetics

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.302 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033326.3. 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_033326.3		c.-5+12561C>T		intron	N/A	NP_201583.2	P35712-3
	SOX6	NM_001367872.1		c.-4-122502C>T		intron	N/A	NP_001354801.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SOX6	ENST00000396356.7	TSL:1	c.-5+12561C>T		intron	N/A	ENSP00000379644.3	P35712-3
	SOX6	ENST00000887067.1		c.-5+12561C>T		intron	N/A	ENSP00000557126.1
	SOX6	ENST00000887062.1		c.-5+12561C>T		intron	N/A	ENSP00000557121.1

Frequencies

GnomAD3 genomes AF: 0.287 AC: 43588 AN: 151972 Hom.: 6451 Cov.: 32

Gnomad AFR AF: 0.307

Gnomad AMI AF: 0.193

Gnomad AMR AF: 0.234

Gnomad ASJ AF: 0.349

Gnomad EAS AF: 0.0521

Gnomad SAS AF: 0.192

Gnomad FIN AF: 0.382

Gnomad MID AF: 0.303

Gnomad NFE AF: 0.294

Gnomad OTH AF: 0.293

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

GnomAD4 genome AF: 0.287 AC: 43620 AN: 152090 Hom.: 6457 Cov.: 32 AF XY: 0.286 AC XY: 21249 AN XY: 74336

African (AFR) AF: 0.307 AC: 12722 AN: 41498

American (AMR) AF: 0.234 AC: 3584 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.349 AC: 1212 AN: 3472

East Asian (EAS) AF: 0.0525 AC: 271 AN: 5166

South Asian (SAS) AF: 0.192 AC: 927 AN: 4826

European-Finnish (FIN) AF: 0.382 AC: 4042 AN: 10576

Middle Eastern (MID) AF: 0.305 AC: 89 AN: 292

European-Non Finnish (NFE) AF: 0.294 AC: 19987 AN: 67956

Other (OTH) AF: 0.290 AC: 610 AN: 2104

Alfa AF: 0.291 Hom.: 28797

Bravo AF: 0.278

Asia WGS AF: 0.134 AC: 468 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.6
DANN	Benign	0.61
PhyloP100		0.39
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1354329; hg19: chr11-16485301;