11-16375514-A-G

Position:

• chr11-16375514-A-G

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
SOX6	NM_001145811.2	c.-5+33184T>C		intron_variant			NP_001139283.1
SOX6	NM_001145819.2	c.-5+27286T>C		intron_variant			NP_001139291.2
SOX6	NM_001367872.1	c.-4-34262T>C		intron_variant			NP_001354801.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SOX6	ENST00000396356.7	c.-4-34262T>C		intron_variant		1		ENSP00000379644	P4
SOX6	ENST00000527619.6	c.-5+27145T>C		intron_variant		1		ENSP00000434455	A2
SOX6	ENST00000528429.5	c.-5+27286T>C		intron_variant		1		ENSP00000433233	A2

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

Gnomad4 AFR AF: 0.202

Gnomad4 AMR AF: 0.310

Gnomad4 ASJ AF: 0.111

Gnomad4 EAS AF: 0.307

Gnomad4 SAS AF: 0.194

Gnomad4 FIN AF: 0.141

Gnomad4 NFE AF: 0.211

Gnomad4 OTH AF: 0.206

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs297335; hg19: chr11-16397060;