rs1065024

Positions:

• chr11-15967804-A-G

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SOX6	NM_001367873.1	c.*5005T>C		3_prime_UTR_variant	16/16	ENST00000683767.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SOX6	ENST00000683767.1	c.*5005T>C		3_prime_UTR_variant	16/16		NM_001367873.1	A2
SOX6	ENST00000396356.7	c.*5005T>C		3_prime_UTR_variant	16/16	1		P4
SOX6	ENST00000316399.10	c.*5005T>C		3_prime_UTR_variant	15/15	5		P4
SOX6	ENST00000655819.1	c.*5005T>C		3_prime_UTR_variant	15/15			A2

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

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.333

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

Gnomad4 AFR AF: 0.506

Gnomad4 AMR AF: 0.231

Gnomad4 ASJ AF: 0.130

Gnomad4 EAS AF: 0.507

Gnomad4 SAS AF: 0.179

Gnomad4 FIN AF: 0.135

Gnomad4 NFE AF: 0.124

Gnomad4 OTH AF: 0.226

Alfa AF: 0.162 Hom.: 2881

Bravo AF: 0.279

Asia WGS AF: 0.348 AC: 1210 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs1065024; hg19: chr11-15989350;