rs11023944

Variant names:

• chr11-16439361-T-G
• rs11023944
• ENST00000396356.7:c.-5+36954A>C

Variant summary

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

The ENST00000396356.7(SOX6):​c.-5+36954A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.359 in 152,016 control chromosomes in the GnomAD database, including 10,378 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 0.36 (10378 hom., cov: 32)
• Consequence: SOX6 ENST00000396356.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.472
• Publications: 3 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=-0.57).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.523 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SOX6	NM_033326.3	c.-5+36954A>C		intron_variant	Intron 1 of 15		NP_201583.2
SOX6	NM_001367872.1	c.-4-98109A>C		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+36954A>C		intron_variant	Intron 1 of 15	1		ENSP00000379644.3
SOX6	ENST00000530378.5	n.-5+36954A>C		intron_variant	Intron 5 of 9	2		ENSP00000432577.1
SOX6	ENST00000533658.5	n.333+26340A>C		intron_variant	Intron 4 of 5	2

Frequencies

GnomAD3 genomes AF: 0.359 AC: 54490 AN: 151900 Hom.: 10350 Cov.: 32

Gnomad AFR AF: 0.480

Gnomad AMI AF: 0.275

Gnomad AMR AF: 0.317

Gnomad ASJ AF: 0.318

Gnomad EAS AF: 0.540

Gnomad SAS AF: 0.489

Gnomad FIN AF: 0.289

Gnomad MID AF: 0.410

Gnomad NFE AF: 0.285

Gnomad OTH AF: 0.369

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

GnomAD4 genome AF: 0.359 AC: 54559 AN: 152016 Hom.: 10378 Cov.: 32 AF XY: 0.363 AC XY: 26957 AN XY: 74294

African (AFR) AF: 0.480 AC: 19901 AN: 41434

American (AMR) AF: 0.317 AC: 4842 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.318 AC: 1100 AN: 3464

East Asian (EAS) AF: 0.540 AC: 2785 AN: 5162

South Asian (SAS) AF: 0.489 AC: 2356 AN: 4816

European-Finnish (FIN) AF: 0.289 AC: 3061 AN: 10584

Middle Eastern (MID) AF: 0.417 AC: 121 AN: 290

European-Non Finnish (NFE) AF: 0.285 AC: 19344 AN: 67964

Other (OTH) AF: 0.379 AC: 798 AN: 2108

Alfa AF: 0.325 Hom.: 3855

Bravo AF: 0.368

Asia WGS AF: 0.527 AC: 1827 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	7.1
DANN	Benign	0.70
PhyloP100		0.47
Mutation Taster		=99/1	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs11023944; hg19: chr11-16460908;