NM_001367872.1:c.-184-3516G>A

Variant names:

• chr11-16615776-C-T
• rs6486303
• NM_001367872.1:c.-184-3516G>A

Variant summary

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

The NM_001367872.1(SOX6):​c.-184-3516G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.268 in 151,916 control chromosomes in the GnomAD database, including 6,223 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 0.27 (6223 hom., cov: 32)
• Consequence: SOX6 NM_001367872.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.587
• Publications: 2 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]

C11orf58 (HGNC:16990): (chromosome 11 open reading frame 58)

LOC105376571 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.516 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SOX6	NM_001367872.1	c.-184-3516G>A		intron_variant	Intron 2 of 16		NP_001354801.1
LOC105376571	XR_931085.3	n.405+2562C>T		intron_variant	Intron 1 of 2
LOC105376571	XR_931086.3	n.1197+1276C>T		intron_variant	Intron 2 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SOX6	ENST00000524520.5	n.430-3516G>A		intron_variant	Intron 3 of 5	5
SOX6	ENST00000525259.1	n.344-3516G>A		intron_variant	Intron 3 of 4	4
C11orf58	ENST00000527893.5	n.83+2562C>T		intron_variant	Intron 1 of 3	4
SOX6	ENST00000530378.5	n.-258-3516G>A		intron_variant	Intron 3 of 9	2		ENSP00000432577.1

Frequencies

GnomAD3 genomes AF: 0.268 AC: 40746 AN: 151798 Hom.: 6216 Cov.: 32

Gnomad AFR AF: 0.364

Gnomad AMI AF: 0.210

Gnomad AMR AF: 0.237

Gnomad ASJ AF: 0.288

Gnomad EAS AF: 0.533

Gnomad SAS AF: 0.476

Gnomad FIN AF: 0.141

Gnomad MID AF: 0.399

Gnomad NFE AF: 0.201

Gnomad OTH AF: 0.277

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

GnomAD4 genome AF: 0.268 AC: 40776 AN: 151916 Hom.: 6223 Cov.: 32 AF XY: 0.269 AC XY: 19995 AN XY: 74242

African (AFR) AF: 0.364 AC: 15059 AN: 41412

American (AMR) AF: 0.237 AC: 3618 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.288 AC: 1000 AN: 3472

East Asian (EAS) AF: 0.532 AC: 2755 AN: 5174

South Asian (SAS) AF: 0.475 AC: 2289 AN: 4814

European-Finnish (FIN) AF: 0.141 AC: 1483 AN: 10538

Middle Eastern (MID) AF: 0.395 AC: 116 AN: 294

European-Non Finnish (NFE) AF: 0.201 AC: 13665 AN: 67936

Other (OTH) AF: 0.285 AC: 600 AN: 2102

Alfa AF: 0.230 Hom.: 784

Bravo AF: 0.281

Asia WGS AF: 0.523 AC: 1813 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.5
DANN	Benign	0.71
PhyloP100		-0.59

Splicing

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

Other links and lift over

dbSNP: rs6486303; hg19: chr11-16637323;