rs16932445

Variant names:

• chr11-16013083-G-A
• rs16932445
• NM_001367873.1:c.1732+1859C>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.1732+1859C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0915 in 151,828 control chromosomes in the GnomAD database, including 1,310 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 0.091 (1310 hom., cov: 32)
• Consequence: SOX6 NM_001367873.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.913
• Publications: 1 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=-0.76).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.342 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SOX6	NM_001367873.1	c.1732+1859C>T		intron_variant	Intron 13 of 15	ENST00000683767.1	NP_001354802.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SOX6	ENST00000683767.1	c.1732+1859C>T		intron_variant	Intron 13 of 15		NM_001367873.1	ENSP00000507545.1

Frequencies

GnomAD3 genomes AF: 0.0914 AC: 13869 AN: 151708 Hom.: 1305 Cov.: 32

Gnomad AFR AF: 0.195

Gnomad AMI AF: 0.0252

Gnomad AMR AF: 0.123

Gnomad ASJ AF: 0.0557

Gnomad EAS AF: 0.356

Gnomad SAS AF: 0.0462

Gnomad FIN AF: 0.0849

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.00917

Gnomad OTH AF: 0.0718

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

GnomAD4 genome AF: 0.0915 AC: 13892 AN: 151828 Hom.: 1310 Cov.: 32 AF XY: 0.0955 AC XY: 7083 AN XY: 74172

African (AFR) AF: 0.195 AC: 8090 AN: 41422

American (AMR) AF: 0.123 AC: 1871 AN: 15214

Ashkenazi Jewish (ASJ) AF: 0.0557 AC: 193 AN: 3468

East Asian (EAS) AF: 0.356 AC: 1818 AN: 5112

South Asian (SAS) AF: 0.0452 AC: 218 AN: 4818

European-Finnish (FIN) AF: 0.0849 AC: 895 AN: 10548

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.00917 AC: 623 AN: 67928

Other (OTH) AF: 0.0715 AC: 151 AN: 2112

Alfa AF: 0.0628 Hom.: 99

Bravo AF: 0.106

Asia WGS AF: 0.202 AC: 701 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	7.5
DANN	Benign	0.73
PhyloP100		0.91
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: rs16932445; hg19: chr11-16034629;