NM_001367873.1:c.445+10443A>G

Variant names:

• chr11-16308003-T-C
• rs297366
• NM_001367873.1:c.445+10443A>G

Variant summary

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

The NM_001367873.1(SOX6):​c.445+10443A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.443 in 151,966 control chromosomes in the GnomAD database, including 15,184 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 0.44 (15184 hom., cov: 32)
• Consequence: SOX6 NM_001367873.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.310
• Publications: 5 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=-0.73).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.462 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SOX6	NM_001367873.1	c.445+10443A>G		intron_variant	Intron 3 of 15	ENST00000683767.1	NP_001354802.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SOX6	ENST00000683767.1	c.445+10443A>G		intron_variant	Intron 3 of 15		NM_001367873.1	ENSP00000507545.1

Frequencies

GnomAD3 genomes AF: 0.443 AC: 67205 AN: 151848 Hom.: 15178 Cov.: 32

Gnomad AFR AF: 0.447

Gnomad AMI AF: 0.408

Gnomad AMR AF: 0.396

Gnomad ASJ AF: 0.395

Gnomad EAS AF: 0.478

Gnomad SAS AF: 0.322

Gnomad FIN AF: 0.636

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.430

Gnomad OTH AF: 0.445

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

GnomAD4 genome AF: 0.443 AC: 67250 AN: 151966 Hom.: 15184 Cov.: 32 AF XY: 0.448 AC XY: 33286 AN XY: 74292

African (AFR) AF: 0.446 AC: 18508 AN: 41462

American (AMR) AF: 0.395 AC: 6031 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.395 AC: 1368 AN: 3466

East Asian (EAS) AF: 0.478 AC: 2466 AN: 5164

South Asian (SAS) AF: 0.322 AC: 1549 AN: 4812

European-Finnish (FIN) AF: 0.636 AC: 6705 AN: 10548

Middle Eastern (MID) AF: 0.384 AC: 113 AN: 294

European-Non Finnish (NFE) AF: 0.430 AC: 29191 AN: 67950

Other (OTH) AF: 0.449 AC: 948 AN: 2110

Alfa AF: 0.426 Hom.: 8005

Bravo AF: 0.425

Asia WGS AF: 0.449 AC: 1560 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	13
DANN	Benign	0.87
PhyloP100		0.31
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs297366; hg19: chr11-16329549;