rs17463551

Positions:

• chr11-16409651-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000396356.7(SOX6):​c.-5+66664G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0564 in 151,816 control chromosomes in the GnomAD database, including 304 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 0.056 (304 hom., cov: 32)
• Consequence: SOX6 ENST00000396356.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0180

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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.083 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SOX6	NM_001367872.1	c.-4-68399G>A		intron_variant
SOX6	NM_033326.3	c.-5+66664G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SOX6	ENST00000396356.7	c.-5+66664G>A		intron_variant		1		P4
SOX6	ENST00000529469.1	c.-5+24493G>A		intron_variant		4
SOX6	ENST00000530378.5	c.-5+66664G>A		intron_variant, NMD_transcript_variant		2
SOX6	ENST00000533658.5	n.333+56050G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0564 AC: 8559 AN: 151698 Hom.: 304 Cov.: 32

Gnomad AFR AF: 0.0146

Gnomad AMI AF: 0.0384

Gnomad AMR AF: 0.0393

Gnomad ASJ AF: 0.0481

Gnomad EAS AF: 0.000580

Gnomad SAS AF: 0.0154

Gnomad FIN AF: 0.116

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0847

Gnomad OTH AF: 0.0513

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

GnomAD4 genome AF: 0.0564 AC: 8561 AN: 151816 Hom.: 304 Cov.: 32 AF XY: 0.0563 AC XY: 4180 AN XY: 74184

Gnomad4 AFR AF: 0.0145

Gnomad4 AMR AF: 0.0393

Gnomad4 ASJ AF: 0.0481

Gnomad4 EAS AF: 0.000582

Gnomad4 SAS AF: 0.0152

Gnomad4 FIN AF: 0.116

Gnomad4 NFE AF: 0.0848

Gnomad4 OTH AF: 0.0508

Alfa AF: 0.0758 Hom.: 669

Bravo AF: 0.0491

Asia WGS AF: 0.00811 AC: 28 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.4
DANN	Benign	0.38

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs17463551; hg19: chr11-16431197;