11-16269587-A-T

Variant names:

• chr11-16269587-A-T
• rs12274377
• NM_001367873.1:c.446-34916T>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 publications found

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]

SOX6 Gene-Disease associations (from GenCC):

• Tolchin-Le Caignec syndrome

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, PanelApp Australia, G2P, Illumina

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001367873.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SOX6	NM_001367873.1	MANE Select	c.446-34916T>A		intron	N/A	NP_001354802.1
	SOX6	NM_001145819.2		c.446-34916T>A		intron	N/A	NP_001139291.2
	SOX6	NM_033326.3		c.446-34916T>A		intron	N/A	NP_201583.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SOX6	ENST00000683767.1	MANE Select	c.446-34916T>A		intron	N/A	ENSP00000507545.1
	SOX6	ENST00000528429.5	TSL:1	c.446-34916T>A		intron	N/A	ENSP00000433233.1
	SOX6	ENST00000396356.7	TSL:1	c.446-34916T>A		intron	N/A	ENSP00000379644.3

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

African (AFR) AF: 0.269 AC: 11100 AN: 41326

American (AMR) AF: 0.378 AC: 5701 AN: 15080

Ashkenazi Jewish (ASJ) AF: 0.417 AC: 1439 AN: 3452

East Asian (EAS) AF: 0.479 AC: 2464 AN: 5142

South Asian (SAS) AF: 0.323 AC: 1557 AN: 4816

European-Finnish (FIN) AF: 0.634 AC: 6544 AN: 10320

Middle Eastern (MID) AF: 0.398 AC: 117 AN: 294

European-Non Finnish (NFE) AF: 0.430 AC: 28799 AN: 67016

Other (OTH) AF: 0.420 AC: 880 AN: 2096

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	5.2
DANN	Benign	0.61
PhyloP100		0.98
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12274377; hg19: chr11-16291133;