rs10128558

chr11-16326884-C-Gchr11-16326884-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001367873.1(SOX6):c.238-8231G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.102 in 152,186 control chromosomes in the GnomAD database, including 844 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 0.10 (844 hom., cov: 32)
• Consequence: SOX6 NM_001367873.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0550

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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.114 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SOX6	NM_001367873.1	c.238-8231G>C		intron_variant		ENST00000683767.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SOX6	ENST00000683767.1	c.238-8231G>C		intron_variant			NM_001367873.1	A2

Frequencies

GnomAD3 genomes AF: 0.102 AC: 15498 AN: 152068 Hom.: 842 Cov.: 32

Gnomad AFR AF: 0.117

Gnomad AMI AF: 0.166

Gnomad AMR AF: 0.0884

Gnomad ASJ AF: 0.0954

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.0334

Gnomad FIN AF: 0.0858

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.110

Gnomad OTH AF: 0.108

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

GnomAD4 genome AF: 0.102 AC: 15510 AN: 152186 Hom.: 844 Cov.: 32 AF XY: 0.0988 AC XY: 7353 AN XY: 74400

Gnomad4 AFR AF: 0.117

Gnomad4 AMR AF: 0.0884

Gnomad4 ASJ AF: 0.0954

Gnomad4 EAS AF: 0.000387

Gnomad4 SAS AF: 0.0336

Gnomad4 FIN AF: 0.0858

Gnomad4 NFE AF: 0.110

Gnomad4 OTH AF: 0.107

Alfa AF: 0.0506 Hom.: 47

Bravo AF: 0.105

Asia WGS AF: 0.0270 AC: 92 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	3.4
Dann	Benign	0.42

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

Publications

LitVar

Other links and lift over

dbSNP: rs10128558; hg19: chr11-16348430;