11-16269587-A-T

Position:

• chr11-16269587-A-T

Variant summary

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

The NM_001367873.1(SOX6):​c.446-34916T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.392 in 150,450 control chromosomes in the GnomAD database, including 12,300 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 0.39 (12300 hom., cov: 30)
• Consequence: SOX6 NM_001367873.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.976

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.463 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SOX6	NM_001367873.1	c.446-34916T>A		intron_variant		ENST00000683767.1	NP_001354802.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SOX6	ENST00000683767.1	c.446-34916T>A		intron_variant			NM_001367873.1	ENSP00000507545.1

Frequencies

GnomAD3 genomes AF: 0.392 AC: 58946 AN: 150332 Hom.: 12300 Cov.: 30

Gnomad AFR AF: 0.269

Gnomad AMI AF: 0.407

Gnomad AMR AF: 0.378

Gnomad ASJ AF: 0.417

Gnomad EAS AF: 0.480

Gnomad SAS AF: 0.324

Gnomad FIN AF: 0.634

Gnomad MID AF: 0.386

Gnomad NFE AF: 0.430

Gnomad OTH AF: 0.416

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

GnomAD4 genome AF: 0.392 AC: 58971 AN: 150450 Hom.: 12300 Cov.: 30 AF XY: 0.400 AC XY: 29420 AN XY: 73522

Gnomad4 AFR AF: 0.269

Gnomad4 AMR AF: 0.378

Gnomad4 ASJ AF: 0.417

Gnomad4 EAS AF: 0.479

Gnomad4 SAS AF: 0.323

Gnomad4 FIN AF: 0.634

Gnomad4 NFE AF: 0.430

Gnomad4 OTH AF: 0.420

Alfa AF: 0.303 Hom.: 887

Bravo AF: 0.368

Asia WGS AF: 0.441 AC: 1521 AN: 3454

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	5.2
DANN	Benign	0.61

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: rs12274377; hg19: chr11-16291133;