chr11-16231436-T-C

Position:

• chr11-16231436-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.535+3146A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.206 in 151,638 control chromosomes in the GnomAD database, including 3,888 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 0.21 (3888 hom., cov: 32)
• Consequence: SOX6 NM_001367873.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.924

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.313 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SOX6	NM_001367873.1	c.535+3146A>G		intron_variant		ENST00000683767.1	NP_001354802.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SOX6	ENST00000683767.1	c.535+3146A>G		intron_variant			NM_001367873.1	ENSP00000507545	A2

Frequencies

GnomAD3 genomes AF: 0.206 AC: 31169 AN: 151520 Hom.: 3885 Cov.: 32

Gnomad AFR AF: 0.0708

Gnomad AMI AF: 0.228

Gnomad AMR AF: 0.319

Gnomad ASJ AF: 0.173

Gnomad EAS AF: 0.246

Gnomad SAS AF: 0.238

Gnomad FIN AF: 0.201

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.259

Gnomad OTH AF: 0.208

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

GnomAD4 genome AF: 0.206 AC: 31173 AN: 151638 Hom.: 3888 Cov.: 32 AF XY: 0.206 AC XY: 15248 AN XY: 74108

Gnomad4 AFR AF: 0.0706

Gnomad4 AMR AF: 0.320

Gnomad4 ASJ AF: 0.173

Gnomad4 EAS AF: 0.246

Gnomad4 SAS AF: 0.237

Gnomad4 FIN AF: 0.201

Gnomad4 NFE AF: 0.259

Gnomad4 OTH AF: 0.204

Alfa AF: 0.210 Hom.: 572

Bravo AF: 0.208

Asia WGS AF: 0.189 AC: 656 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.60
DANN	Benign	0.72

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: rs7927191; hg19: chr11-16252982;