rs297325

Variant names:

• chr11-16368048-T-C
• rs297325
• ENST00000528429.5:c.-4-26796A>G

Your query was ambiguous. Multiple possible variants found:

• chr11-16368048-T-C
• chr11-16368048-T-G

Variant summary

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

The ENST00000528429.5(SOX6):​c.-4-26796A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.191 in 152,070 control chromosomes in the GnomAD database, including 3,155 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 0.19 (3155 hom., cov: 32)
• Consequence: SOX6 ENST00000528429.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.268
• Publications: 22 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=-1.04).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.304 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SOX6	NM_001145819.2	c.-4-26796A>G		intron_variant	Intron 1 of 15		NP_001139291.2
SOX6	NM_033326.3	c.-4-26796A>G		intron_variant	Intron 1 of 15		NP_201583.2
SOX6	NM_001145811.2	c.-4-26796A>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.-4-26796A>G		intron_variant	Intron 1 of 15	1		ENSP00000433233.1
SOX6	ENST00000396356.7	c.-4-26796A>G		intron_variant	Intron 1 of 15	1		ENSP00000379644.3
SOX6	ENST00000527619.6	c.-4-26796A>G		intron_variant	Intron 1 of 14	1		ENSP00000434455.2

Frequencies

GnomAD3 genomes AF: 0.191 AC: 28984 AN: 151952 Hom.: 3159 Cov.: 32

Gnomad AFR AF: 0.103

Gnomad AMI AF: 0.138

Gnomad AMR AF: 0.311

Gnomad ASJ AF: 0.117

Gnomad EAS AF: 0.309

Gnomad SAS AF: 0.198

Gnomad FIN AF: 0.147

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.219

Gnomad OTH AF: 0.200

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

GnomAD4 genome AF: 0.191 AC: 28989 AN: 152070 Hom.: 3155 Cov.: 32 AF XY: 0.192 AC XY: 14302 AN XY: 74318

African (AFR) AF: 0.103 AC: 4273 AN: 41516

American (AMR) AF: 0.311 AC: 4740 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.117 AC: 406 AN: 3468

East Asian (EAS) AF: 0.309 AC: 1594 AN: 5158

South Asian (SAS) AF: 0.199 AC: 961 AN: 4818

European-Finnish (FIN) AF: 0.147 AC: 1561 AN: 10600

Middle Eastern (MID) AF: 0.143 AC: 42 AN: 294

European-Non Finnish (NFE) AF: 0.219 AC: 14870 AN: 67950

Other (OTH) AF: 0.197 AC: 416 AN: 2112

Alfa AF: 0.209 Hom.: 10911

Bravo AF: 0.198

Asia WGS AF: 0.215 AC: 745 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.59
DANN	Benign	0.18
PhyloP100		-0.27
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: rs297325; hg19: chr11-16389594;