rs1065024

Variant names:

• chr11-15967804-A-G
• rs1065024
• NM_001367873.1:c.*5005T>C

Variant summary

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

The NM_001367873.1(SOX6):​c.*5005T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.255 in 151,944 control chromosomes in the GnomAD database, including 7,129 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 0.26 (7129 hom., cov: 32)
  • Exomes 𝑓: 0.25 (0 hom.)
• Consequence: SOX6 NM_001367873.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.61
• Publications: 7 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: G2P, Illumina, Ambry Genetics, PanelApp Australia, Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.5 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001367873.1. 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_001367873.1	MANE Select	c.*5005T>C		3_prime_UTR	Exon 16 of 16	NP_001354802.1	P35712-1
	SOX6	NM_001145819.2		c.*5005T>C		3_prime_UTR	Exon 16 of 16	NP_001139291.2	P35712-1
	SOX6	NM_033326.3		c.*5005T>C		3_prime_UTR	Exon 16 of 16	NP_201583.2	P35712-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SOX6	ENST00000683767.1	MANE Select	c.*5005T>C		3_prime_UTR	Exon 16 of 16	ENSP00000507545.1	P35712-1
	SOX6	ENST00000396356.7	TSL:1	c.*5005T>C		3_prime_UTR	Exon 16 of 16	ENSP00000379644.3	P35712-3
	SOX6	ENST00000316399.10	TSL:5	c.*5005T>C		3_prime_UTR	Exon 15 of 15	ENSP00000324948.6	P35712-3

Frequencies

GnomAD3 genomes AF: 0.255 AC: 38739 AN: 151816 Hom.: 7103 Cov.: 32

Gnomad AFR AF: 0.505

Gnomad AMI AF: 0.133

Gnomad AMR AF: 0.231

Gnomad ASJ AF: 0.130

Gnomad EAS AF: 0.507

Gnomad SAS AF: 0.180

Gnomad FIN AF: 0.135

Gnomad MID AF: 0.118

Gnomad NFE AF: 0.124

Gnomad OTH AF: 0.227

GnomAD4 exome AF: 0.250 AC: 2 AN: 8 Hom.: 0 Cov.: 0 AF XY: 0.333 AC XY: 2 AN XY: 6

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.333 AC: 2 AN: 6

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.255 AC: 38808 AN: 151936 Hom.: 7129 Cov.: 32 AF XY: 0.255 AC XY: 18974 AN XY: 74272

African (AFR) AF: 0.506 AC: 20912 AN: 41358

American (AMR) AF: 0.231 AC: 3524 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.130 AC: 450 AN: 3470

East Asian (EAS) AF: 0.507 AC: 2598 AN: 5120

South Asian (SAS) AF: 0.179 AC: 862 AN: 4812

European-Finnish (FIN) AF: 0.135 AC: 1430 AN: 10584

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.124 AC: 8400 AN: 68004

Other (OTH) AF: 0.226 AC: 477 AN: 2112

Alfa AF: 0.172 Hom.: 4552

Bravo AF: 0.279

Asia WGS AF: 0.348 AC: 1210 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	9.6
DANN	Benign	0.68
PhyloP100		1.6
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1065024;

hg19: chr11-15989350;