11-16241328-C-T

Variant names:

• chr11-16241328-C-T
• rs1837096
• NM_001367873.1:c.446-6657G>A

Variant summary

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

The NM_001367873.1(SOX6):​c.446-6657G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.778 in 151,840 control chromosomes in the GnomAD database, including 46,092 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 0.78 (46092 hom., cov: 30)
• Consequence: SOX6 NM_001367873.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.375
• 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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.796 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SOX6	NM_001367873.1	c.446-6657G>A		intron_variant	Intron 3 of 15	ENST00000683767.1	NP_001354802.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SOX6	ENST00000683767.1	c.446-6657G>A		intron_variant	Intron 3 of 15		NM_001367873.1	ENSP00000507545.1

Frequencies

GnomAD3 genomes AF: 0.778 AC: 118047 AN: 151724 Hom.: 46066 Cov.: 30

Gnomad AFR AF: 0.749

Gnomad AMI AF: 0.782

Gnomad AMR AF: 0.687

Gnomad ASJ AF: 0.843

Gnomad EAS AF: 0.751

Gnomad SAS AF: 0.764

Gnomad FIN AF: 0.866

Gnomad MID AF: 0.791

Gnomad NFE AF: 0.802

Gnomad OTH AF: 0.791

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

GnomAD4 genome AF: 0.778 AC: 118121 AN: 151840 Hom.: 46092 Cov.: 30 AF XY: 0.780 AC XY: 57913 AN XY: 74256

African (AFR) AF: 0.748 AC: 30980 AN: 41394

American (AMR) AF: 0.686 AC: 10428 AN: 15194

Ashkenazi Jewish (ASJ) AF: 0.843 AC: 2923 AN: 3468

East Asian (EAS) AF: 0.751 AC: 3859 AN: 5140

South Asian (SAS) AF: 0.765 AC: 3687 AN: 4818

European-Finnish (FIN) AF: 0.866 AC: 9175 AN: 10590

Middle Eastern (MID) AF: 0.793 AC: 233 AN: 294

European-Non Finnish (NFE) AF: 0.802 AC: 54450 AN: 67924

Other (OTH) AF: 0.794 AC: 1673 AN: 2106

Alfa AF: 0.756 Hom.: 4317

Bravo AF: 0.762

Asia WGS AF: 0.803 AC: 2792 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	6.7
DANN	Benign	0.69
PhyloP100		-0.38
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: rs1837096; hg19: chr11-16262874;