11-16367491-G-C

Variant summary

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

The ENST00000528429.5(SOX6):c.-4-26239C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0718 in 152,078 control chromosomes in the GnomAD database, including 475 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 0.072 (475 hom., cov: 32)
• Consequence: SOX6 ENST00000528429.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.524

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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.179 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SOX6	NM_001145811.2	c.-4-26239C>G		intron_variant
SOX6	NM_001145819.2	c.-4-26239C>G		intron_variant
SOX6	NM_001367872.1	c.-4-26239C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SOX6	ENST00000396356.7	c.-4-26239C>G		intron_variant		1		P4
SOX6	ENST00000527619.6	c.-4-26239C>G		intron_variant		1		A2
SOX6	ENST00000528429.5	c.-4-26239C>G		intron_variant		1		A2

Frequencies

GnomAD3 genomes AF: 0.0718 AC: 10914 AN: 151960 Hom.: 476 Cov.: 32

Gnomad AFR AF: 0.0186

Gnomad AMI AF: 0.0384

Gnomad AMR AF: 0.0834

Gnomad ASJ AF: 0.0542

Gnomad EAS AF: 0.189

Gnomad SAS AF: 0.0911

Gnomad FIN AF: 0.100

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0881

Gnomad OTH AF: 0.0789

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

GnomAD4 genome AF: 0.0718 AC: 10914 AN: 152078 Hom.: 475 Cov.: 32 AF XY: 0.0730 AC XY: 5426 AN XY: 74336

Gnomad4 AFR AF: 0.0185

Gnomad4 AMR AF: 0.0835

Gnomad4 ASJ AF: 0.0542

Gnomad4 EAS AF: 0.189

Gnomad4 SAS AF: 0.0908

Gnomad4 FIN AF: 0.100

Gnomad4 NFE AF: 0.0882

Gnomad4 OTH AF: 0.0786

Alfa AF: 0.0491 Hom.: 61

Bravo AF: 0.0704

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	10
Dann	Benign	0.81

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1503436; hg19: chr11-16389037;