rs297339

Variant names:

• chr11-16382737-T-C
• rs297339
• ENST00000528429.5:c.-5+20063A>G

Variant summary

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

The ENST00000528429.5(SOX6):​c.-5+20063A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.685 in 151,682 control chromosomes in the GnomAD database, including 35,815 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 0.69 (35815 hom., cov: 30)
• Consequence: SOX6 ENST00000528429.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.541
• Publications: 3 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.714 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SOX6	NM_001145819.2	c.-5+20063A>G		intron_variant	Intron 1 of 15		NP_001139291.2
SOX6	NM_033326.3	c.-4-41485A>G		intron_variant	Intron 1 of 15		NP_201583.2
SOX6	NM_001145811.2	c.-5+25961A>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.-5+20063A>G		intron_variant	Intron 1 of 15	1		ENSP00000433233.1
SOX6	ENST00000396356.7	c.-4-41485A>G		intron_variant	Intron 1 of 15	1		ENSP00000379644.3
SOX6	ENST00000527619.6	c.-5+19922A>G		intron_variant	Intron 1 of 14	1		ENSP00000434455.2

Frequencies

GnomAD3 genomes AF: 0.685 AC: 103858 AN: 151564 Hom.: 35777 Cov.: 30

Gnomad AFR AF: 0.656

Gnomad AMI AF: 0.726

Gnomad AMR AF: 0.699

Gnomad ASJ AF: 0.694

Gnomad EAS AF: 0.482

Gnomad SAS AF: 0.541

Gnomad FIN AF: 0.727

Gnomad MID AF: 0.595

Gnomad NFE AF: 0.719

Gnomad OTH AF: 0.671

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

GnomAD4 genome AF: 0.685 AC: 103944 AN: 151682 Hom.: 35815 Cov.: 30 AF XY: 0.682 AC XY: 50530 AN XY: 74134

African (AFR) AF: 0.656 AC: 27164 AN: 41404

American (AMR) AF: 0.699 AC: 10627 AN: 15206

Ashkenazi Jewish (ASJ) AF: 0.694 AC: 2401 AN: 3460

East Asian (EAS) AF: 0.483 AC: 2495 AN: 5168

South Asian (SAS) AF: 0.542 AC: 2610 AN: 4818

European-Finnish (FIN) AF: 0.727 AC: 7675 AN: 10560

Middle Eastern (MID) AF: 0.588 AC: 173 AN: 294

European-Non Finnish (NFE) AF: 0.719 AC: 48748 AN: 67760

Other (OTH) AF: 0.661 AC: 1390 AN: 2102

Alfa AF: 0.695 Hom.: 5062

Bravo AF: 0.680

Asia WGS AF: 0.519 AC: 1802 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.6
DANN	Benign	0.74
PhyloP100		-0.54
PromoterAI		0.0016	Neutral
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: rs297339; hg19: chr11-16404283;