ENST00000528429.5:c.-4-26239C>G

Variant names:

• chr11-16367491-G-C
• rs1503436
• ENST00000528429.5:c.-4-26239C>G

Variant summary

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

The ENST00000528429.5(SOX6):​c.-4-26239C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0718 in 152,078 control chromosomes in the GnomAD database, including 475 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 0.072 (475 hom., cov: 32)
• Consequence: SOX6 ENST00000528429.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.524
• Publications: 4 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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.179 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SOX6	NM_001145819.2	c.-4-26239C>G		intron_variant	Intron 1 of 15		NP_001139291.2
SOX6	NM_033326.3	c.-4-26239C>G		intron_variant	Intron 1 of 15		NP_201583.2
SOX6	NM_001145811.2	c.-4-26239C>G		intron_variant	Intron 1 of 14		NP_001139283.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SOX6	ENST00000528429.5	c.-4-26239C>G		intron_variant	Intron 1 of 15	1		ENSP00000433233.1
SOX6	ENST00000396356.7	c.-4-26239C>G		intron_variant	Intron 1 of 15	1		ENSP00000379644.3
SOX6	ENST00000527619.6	c.-4-26239C>G		intron_variant	Intron 1 of 14	1		ENSP00000434455.2

Frequencies

GnomAD3 genomes AF: 0.0718 AC: 10914 AN: 151960 Hom.: 476 Cov.: 32

Gnomad AFR AF: 0.0186

Gnomad AMI AF: 0.0384

Gnomad AMR AF: 0.0834

Gnomad ASJ AF: 0.0542

Gnomad EAS AF: 0.189

Gnomad SAS AF: 0.0911

Gnomad FIN AF: 0.100

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0881

Gnomad OTH AF: 0.0789

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

GnomAD4 genome AF: 0.0718 AC: 10914 AN: 152078 Hom.: 475 Cov.: 32 AF XY: 0.0730 AC XY: 5426 AN XY: 74336

African (AFR) AF: 0.0185 AC: 769 AN: 41486

American (AMR) AF: 0.0835 AC: 1274 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.0542 AC: 188 AN: 3468

East Asian (EAS) AF: 0.189 AC: 975 AN: 5164

South Asian (SAS) AF: 0.0908 AC: 437 AN: 4814

European-Finnish (FIN) AF: 0.100 AC: 1061 AN: 10586

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0882 AC: 5996 AN: 67986

Other (OTH) AF: 0.0786 AC: 166 AN: 2112

Alfa AF: 0.0491 Hom.: 61

Bravo AF: 0.0704

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	10
DANN	Benign	0.81
PhyloP100		0.52
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs1503436; hg19: chr11-16389037;