rs10500830

Variant names:

• chr11-16463704-G-A
• rs10500830
• ENST00000396356.7:c.-5+12611C>T

Variant summary

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

The ENST00000396356.7(SOX6):​c.-5+12611C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.173 in 152,098 control chromosomes in the GnomAD database, including 2,759 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 0.17 (2759 hom., cov: 32)
• Consequence: SOX6 ENST00000396356.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0130
• Publications: 6 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.297 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SOX6	NM_033326.3	c.-5+12611C>T		intron_variant	Intron 1 of 15		NP_201583.2
SOX6	NM_001367872.1	c.-4-122452C>T		intron_variant	Intron 3 of 16		NP_001354801.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SOX6	ENST00000396356.7	c.-5+12611C>T		intron_variant	Intron 1 of 15	1		ENSP00000379644.3
SOX6	ENST00000530378.5	n.-5+12611C>T		intron_variant	Intron 5 of 9	2		ENSP00000432577.1
SOX6	ENST00000533658.5	n.333+1997C>T		intron_variant	Intron 4 of 5	2

Frequencies

GnomAD3 genomes AF: 0.173 AC: 26332 AN: 151978 Hom.: 2761 Cov.: 32

Gnomad AFR AF: 0.0717

Gnomad AMI AF: 0.143

Gnomad AMR AF: 0.305

Gnomad ASJ AF: 0.110

Gnomad EAS AF: 0.284

Gnomad SAS AF: 0.194

Gnomad FIN AF: 0.127

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.207

Gnomad OTH AF: 0.173

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

GnomAD4 genome AF: 0.173 AC: 26333 AN: 152098 Hom.: 2759 Cov.: 32 AF XY: 0.175 AC XY: 13002 AN XY: 74368

African (AFR) AF: 0.0716 AC: 2974 AN: 41510

American (AMR) AF: 0.305 AC: 4653 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.110 AC: 383 AN: 3470

East Asian (EAS) AF: 0.284 AC: 1463 AN: 5160

South Asian (SAS) AF: 0.194 AC: 937 AN: 4818

European-Finnish (FIN) AF: 0.127 AC: 1344 AN: 10590

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.207 AC: 14052 AN: 67954

Other (OTH) AF: 0.170 AC: 360 AN: 2116

Alfa AF: 0.183 Hom.: 506

Bravo AF: 0.182

Asia WGS AF: 0.198 AC: 685 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.4
DANN	Benign	0.62
PhyloP100		-0.013
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: rs10500830; hg19: chr11-16485251;