chr11-16367738-G-A

Variant names:

• chr11-16367738-G-A
• rs297324
• ENST00000528429.5:c.-4-26486C>T

Variant summary

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

The ENST00000528429.5(SOX6):​c.-4-26486C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.628 in 151,970 control chromosomes in the GnomAD database, including 30,878 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 0.63 (30878 hom., cov: 32)
• Consequence: SOX6 ENST00000528429.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.212
• 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=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.713 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SOX6	NM_001145819.2	c.-4-26486C>T		intron_variant	Intron 1 of 15		NP_001139291.2
SOX6	NM_033326.3	c.-4-26486C>T		intron_variant	Intron 1 of 15		NP_201583.2
SOX6	NM_001145811.2	c.-4-26486C>T		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.-4-26486C>T		intron_variant	Intron 1 of 15	1		ENSP00000433233.1
SOX6	ENST00000396356.7	c.-4-26486C>T		intron_variant	Intron 1 of 15	1		ENSP00000379644.3
SOX6	ENST00000527619.6	c.-4-26486C>T		intron_variant	Intron 1 of 14	1		ENSP00000434455.2

Frequencies

GnomAD3 genomes AF: 0.628 AC: 95395 AN: 151852 Hom.: 30866 Cov.: 32

Gnomad AFR AF: 0.471

Gnomad AMI AF: 0.726

Gnomad AMR AF: 0.664

Gnomad ASJ AF: 0.677

Gnomad EAS AF: 0.460

Gnomad SAS AF: 0.509

Gnomad FIN AF: 0.728

Gnomad MID AF: 0.580

Gnomad NFE AF: 0.718

Gnomad OTH AF: 0.624

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

GnomAD4 genome AF: 0.628 AC: 95438 AN: 151970 Hom.: 30878 Cov.: 32 AF XY: 0.626 AC XY: 46452 AN XY: 74260

African (AFR) AF: 0.471 AC: 19514 AN: 41434

American (AMR) AF: 0.664 AC: 10128 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.677 AC: 2346 AN: 3466

East Asian (EAS) AF: 0.460 AC: 2372 AN: 5154

South Asian (SAS) AF: 0.510 AC: 2453 AN: 4814

European-Finnish (FIN) AF: 0.728 AC: 7687 AN: 10562

Middle Eastern (MID) AF: 0.572 AC: 166 AN: 290

European-Non Finnish (NFE) AF: 0.718 AC: 48814 AN: 67982

Other (OTH) AF: 0.615 AC: 1297 AN: 2108

Alfa AF: 0.665 Hom.: 34472

Bravo AF: 0.614

Asia WGS AF: 0.472 AC: 1642 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.5
DANN	Benign	0.40
PhyloP100		0.21
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: rs297324; hg19: chr11-16389284;