rs297366

chr11-16308003-T-C

Variant summary

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

The NM_001367873.1(SOX6):c.445+10443A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.443 in 151,966 control chromosomes in the GnomAD database, including 15,184 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 0.44 (15184 hom., cov: 32)
• Consequence: SOX6 NM_001367873.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.310

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=-0.73).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.462 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SOX6	NM_001367873.1	c.445+10443A>G		intron_variant		ENST00000683767.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SOX6	ENST00000683767.1	c.445+10443A>G		intron_variant			NM_001367873.1	A2

Frequencies

GnomAD3 genomes AF: 0.443 AC: 67205 AN: 151848 Hom.: 15178 Cov.: 32

Gnomad AFR AF: 0.447

Gnomad AMI AF: 0.408

Gnomad AMR AF: 0.396

Gnomad ASJ AF: 0.395

Gnomad EAS AF: 0.478

Gnomad SAS AF: 0.322

Gnomad FIN AF: 0.636

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.430

Gnomad OTH AF: 0.445

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

GnomAD4 genome AF: 0.443 AC: 67250 AN: 151966 Hom.: 15184 Cov.: 32 AF XY: 0.448 AC XY: 33286 AN XY: 74292

Gnomad4 AFR AF: 0.446

Gnomad4 AMR AF: 0.395

Gnomad4 ASJ AF: 0.395

Gnomad4 EAS AF: 0.478

Gnomad4 SAS AF: 0.322

Gnomad4 FIN AF: 0.636

Gnomad4 NFE AF: 0.430

Gnomad4 OTH AF: 0.449

Alfa AF: 0.427 Hom.: 7260

Bravo AF: 0.425

Asia WGS AF: 0.449 AC: 1560 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
Cadd	Benign	13
Dann	Benign	0.87

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: rs297366; hg19: chr11-16329549;