rs10128558

Variant names:

• chr11-16326884-C-G
• rs10128558
• NM_001367873.1:c.238-8231G>C

Your query was ambiguous. Multiple possible variants found:

• chr11-16326884-C-G
• chr11-16326884-C-T

Variant summary

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

The NM_001367873.1(SOX6):​c.238-8231G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.102 in 152,186 control chromosomes in the GnomAD database, including 844 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 0.10 (844 hom., cov: 32)
• Consequence: SOX6 NM_001367873.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0550
• Publications: 0 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.114 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SOX6	NM_001367873.1	c.238-8231G>C		intron_variant	Intron 2 of 15	ENST00000683767.1	NP_001354802.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SOX6	ENST00000683767.1	c.238-8231G>C		intron_variant	Intron 2 of 15		NM_001367873.1	ENSP00000507545.1

Frequencies

GnomAD3 genomes AF: 0.102 AC: 15498 AN: 152068 Hom.: 842 Cov.: 32

Gnomad AFR AF: 0.117

Gnomad AMI AF: 0.166

Gnomad AMR AF: 0.0884

Gnomad ASJ AF: 0.0954

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.0334

Gnomad FIN AF: 0.0858

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.110

Gnomad OTH AF: 0.108

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

GnomAD4 genome AF: 0.102 AC: 15510 AN: 152186 Hom.: 844 Cov.: 32 AF XY: 0.0988 AC XY: 7353 AN XY: 74400

African (AFR) AF: 0.117 AC: 4853 AN: 41534

American (AMR) AF: 0.0884 AC: 1349 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.0954 AC: 331 AN: 3470

East Asian (EAS) AF: 0.000387 AC: 2 AN: 5170

South Asian (SAS) AF: 0.0336 AC: 162 AN: 4822

European-Finnish (FIN) AF: 0.0858 AC: 910 AN: 10604

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.110 AC: 7498 AN: 68004

Other (OTH) AF: 0.107 AC: 225 AN: 2112

Alfa AF: 0.0506 Hom.: 47

Bravo AF: 0.105

Asia WGS AF: 0.0270 AC: 92 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.4
DANN	Benign	0.42
PhyloP100		0.055
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: rs10128558; hg19: chr11-16348430;