ENST00000887067.1:c.-78-34922T>C

Variant names:

• chr11-16511310-A-G
• rs4491181
• ENST00000887067.1:c.-78-34922T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000887067.1(SOX6):​c.-78-34922T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.167 in 152,136 control chromosomes in the GnomAD database, including 2,609 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 0.17 (2609 hom., cov: 32)
• Consequence: SOX6 ENST00000887067.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.82
• Publications: 2 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):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• Tolchin-Le Caignec syndrome

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

ENSG00000299978 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.296 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000887067.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SOX6	NM_001367872.1		c.-5+100771T>C		intron	N/A	NP_001354801.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SOX6	ENST00000887067.1		c.-78-34922T>C		intron	N/A	ENSP00000557126.1
	SOX6	ENST00000887062.1		c.-78-34922T>C		intron	N/A	ENSP00000557121.1
	SOX6	ENST00000887072.1		c.-78-34922T>C		intron	N/A	ENSP00000557131.1

Frequencies

GnomAD3 genomes AF: 0.167 AC: 25403 AN: 152018 Hom.: 2611 Cov.: 32

Gnomad AFR AF: 0.0696

Gnomad AMI AF: 0.103

Gnomad AMR AF: 0.303

Gnomad ASJ AF: 0.108

Gnomad EAS AF: 0.286

Gnomad SAS AF: 0.191

Gnomad FIN AF: 0.126

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.196

Gnomad OTH AF: 0.172

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

GnomAD4 genome AF: 0.167 AC: 25404 AN: 152136 Hom.: 2609 Cov.: 32 AF XY: 0.170 AC XY: 12614 AN XY: 74382

African (AFR) AF: 0.0696 AC: 2890 AN: 41550

American (AMR) AF: 0.303 AC: 4630 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.108 AC: 375 AN: 3468

East Asian (EAS) AF: 0.286 AC: 1480 AN: 5172

South Asian (SAS) AF: 0.192 AC: 925 AN: 4818

European-Finnish (FIN) AF: 0.126 AC: 1334 AN: 10610

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.195 AC: 13281 AN: 67942

Other (OTH) AF: 0.169 AC: 357 AN: 2114

Alfa AF: 0.180 Hom.: 991

Bravo AF: 0.176

Asia WGS AF: 0.194 AC: 672 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	17
DANN	Benign	0.84
PhyloP100		1.8

Splicing

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

Other links and lift over

dbSNP: rs4491181; hg19: chr11-16532857;