11-16368186-T-G

Variant names:

• chr11-16368186-T-G
• rs297326
• ENST00000528429.5:c.-4-26934A>C

Variant summary

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

The NM_001145819.2(SOX6):​c.-4-26934A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.673 in 152,004 control chromosomes in the GnomAD database, including 34,687 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 0.67 (34687 hom., cov: 32)
• Consequence: SOX6 NM_001145819.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.637
• 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):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• Tolchin-Le Caignec syndrome

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), Illumina, Ambry Genetics, G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.714 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001145819.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SOX6	NM_001145819.2		c.-4-26934A>C		intron	N/A	NP_001139291.2	P35712-1
	SOX6	NM_033326.3		c.-4-26934A>C		intron	N/A	NP_201583.2	P35712-3
	SOX6	NM_001145811.2		c.-4-26934A>C		intron	N/A	NP_001139283.1	P35712-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SOX6	ENST00000528429.5	TSL:1	c.-4-26934A>C		intron	N/A	ENSP00000433233.1	P35712-1
	SOX6	ENST00000396356.7	TSL:1	c.-4-26934A>C		intron	N/A	ENSP00000379644.3	P35712-3
	SOX6	ENST00000527619.6	TSL:1	c.-4-26934A>C		intron	N/A	ENSP00000434455.2	P35712-4

Frequencies

GnomAD3 genomes AF: 0.673 AC: 102187 AN: 151884 Hom.: 34659 Cov.: 32

Gnomad AFR AF: 0.612

Gnomad AMI AF: 0.726

Gnomad AMR AF: 0.693

Gnomad ASJ AF: 0.692

Gnomad EAS AF: 0.485

Gnomad SAS AF: 0.539

Gnomad FIN AF: 0.726

Gnomad MID AF: 0.595

Gnomad NFE AF: 0.720

Gnomad OTH AF: 0.662

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

GnomAD4 genome AF: 0.673 AC: 102262 AN: 152004 Hom.: 34687 Cov.: 32 AF XY: 0.670 AC XY: 49737 AN XY: 74282

African (AFR) AF: 0.613 AC: 25385 AN: 41438

American (AMR) AF: 0.693 AC: 10572 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.692 AC: 2399 AN: 3466

East Asian (EAS) AF: 0.485 AC: 2504 AN: 5162

South Asian (SAS) AF: 0.539 AC: 2597 AN: 4816

European-Finnish (FIN) AF: 0.726 AC: 7660 AN: 10546

Middle Eastern (MID) AF: 0.588 AC: 173 AN: 294

European-Non Finnish (NFE) AF: 0.720 AC: 48931 AN: 68004

Other (OTH) AF: 0.653 AC: 1380 AN: 2114

Alfa AF: 0.642 Hom.: 3203

Bravo AF: 0.665

Asia WGS AF: 0.518 AC: 1804 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.83
DANN	Benign	0.54
PhyloP100		-0.64
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: rs297326; hg19: chr11-16389732;