chr11-16375514-A-G

Variant names:

• chr11-16375514-A-G
• rs297335
• ENST00000528429.5:c.-5+27286T>C

Variant summary

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

The ENST00000528429.5(SOX6):​c.-5+27286T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.213 in 151,960 control chromosomes in the GnomAD database, including 3,598 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 0.21 (3598 hom., cov: 32)
• Consequence: SOX6 ENST00000528429.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.670
• 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 (AMR) allele frequency at 95% confidence interval = 0.302 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SOX6	NM_001145819.2	c.-5+27286T>C		intron_variant	Intron 1 of 15		NP_001139291.2
SOX6	NM_033326.3	c.-4-34262T>C		intron_variant	Intron 1 of 15		NP_201583.2
SOX6	NM_001145811.2	c.-5+33184T>C		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+27286T>C		intron_variant	Intron 1 of 15	1		ENSP00000433233.1
SOX6	ENST00000396356.7	c.-4-34262T>C		intron_variant	Intron 1 of 15	1		ENSP00000379644.3
SOX6	ENST00000527619.6	c.-5+27145T>C		intron_variant	Intron 1 of 14	1		ENSP00000434455.2

Frequencies

GnomAD3 genomes AF: 0.213 AC: 32346 AN: 151840 Hom.: 3599 Cov.: 32

Gnomad AFR AF: 0.201

Gnomad AMI AF: 0.138

Gnomad AMR AF: 0.309

Gnomad ASJ AF: 0.111

Gnomad EAS AF: 0.307

Gnomad SAS AF: 0.193

Gnomad FIN AF: 0.141

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.211

Gnomad OTH AF: 0.209

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

GnomAD4 genome AF: 0.213 AC: 32376 AN: 151960 Hom.: 3598 Cov.: 32 AF XY: 0.213 AC XY: 15840 AN XY: 74274

African (AFR) AF: 0.202 AC: 8362 AN: 41454

American (AMR) AF: 0.310 AC: 4710 AN: 15218

Ashkenazi Jewish (ASJ) AF: 0.111 AC: 384 AN: 3462

East Asian (EAS) AF: 0.307 AC: 1585 AN: 5168

South Asian (SAS) AF: 0.194 AC: 933 AN: 4820

European-Finnish (FIN) AF: 0.141 AC: 1491 AN: 10574

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.211 AC: 14311 AN: 67950

Other (OTH) AF: 0.206 AC: 434 AN: 2108

Alfa AF: 0.199 Hom.: 388

Bravo AF: 0.226

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.74
DANN	Benign	0.64
PhyloP100		-0.67
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: rs297335; hg19: chr11-16397060;