11-16438013-T-C

Variant names:

• chr11-16438013-T-C
• rs10832606
• ENST00000396356.7:c.-5+38302A>G

Variant summary

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

The ENST00000396356.7(SOX6):​c.-5+38302A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.277 in 151,868 control chromosomes in the GnomAD database, including 6,146 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 0.28 (6146 hom., cov: 31)
• Consequence: SOX6 ENST00000396356.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.314
• 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):

• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.5 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000396356.7. 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_033326.3		c.-5+38302A>G		intron	N/A	NP_201583.2
	SOX6	NM_001367872.1		c.-4-96761A>G		intron	N/A	NP_001354801.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SOX6	ENST00000396356.7	TSL:1	c.-5+38302A>G		intron	N/A	ENSP00000379644.3
	SOX6	ENST00000530378.5	TSL:2	n.-5+38302A>G		intron	N/A	ENSP00000432577.1
	SOX6	ENST00000533658.5	TSL:2	n.333+27688A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.277 AC: 42053 AN: 151748 Hom.: 6137 Cov.: 31

Gnomad AFR AF: 0.204

Gnomad AMI AF: 0.276

Gnomad AMR AF: 0.288

Gnomad ASJ AF: 0.302

Gnomad EAS AF: 0.517

Gnomad SAS AF: 0.459

Gnomad FIN AF: 0.290

Gnomad MID AF: 0.398

Gnomad NFE AF: 0.283

Gnomad OTH AF: 0.302

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

GnomAD4 genome AF: 0.277 AC: 42080 AN: 151868 Hom.: 6146 Cov.: 31 AF XY: 0.283 AC XY: 21021 AN XY: 74224

African (AFR) AF: 0.204 AC: 8458 AN: 41432

American (AMR) AF: 0.288 AC: 4390 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.302 AC: 1048 AN: 3470

East Asian (EAS) AF: 0.517 AC: 2654 AN: 5138

South Asian (SAS) AF: 0.459 AC: 2208 AN: 4814

European-Finnish (FIN) AF: 0.290 AC: 3054 AN: 10548

Middle Eastern (MID) AF: 0.401 AC: 118 AN: 294

European-Non Finnish (NFE) AF: 0.283 AC: 19243 AN: 67904

Other (OTH) AF: 0.312 AC: 656 AN: 2104

Alfa AF: 0.201 Hom.: 629

Bravo AF: 0.275

Asia WGS AF: 0.474 AC: 1640 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.5
DANN	Benign	0.49
PhyloP100		0.31
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: rs10832606; hg19: chr11-16459560;