11-16434247-C-T

Position:

• chr11-16434247-C-T

Variant summary

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

The ENST00000396356.7(SOX6):​c.-5+42068G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.117 in 151,992 control chromosomes in the GnomAD database, including 1,159 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 0.12 (1159 hom., cov: 32)
  • Exomes 𝑓: 0.13 (0 hom.)
• Consequence: SOX6 ENST00000396356.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.06

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.16 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SOX6	NM_001367872.1	c.-4-92995G>A		intron_variant
SOX6	NM_033326.3	c.-5+42068G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SOX6	ENST00000396356.7	c.-5+42068G>A		intron_variant		1		P4
SOX6	ENST00000529469.1	c.-108G>A		5_prime_UTR_variant	1/2	4
SOX6	ENST00000530378.5	c.-5+42068G>A		intron_variant, NMD_transcript_variant		2
SOX6	ENST00000533658.5	n.333+31454G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.117 AC: 17827 AN: 151866 Hom.: 1155 Cov.: 32

Gnomad AFR AF: 0.163

Gnomad AMI AF: 0.0548

Gnomad AMR AF: 0.101

Gnomad ASJ AF: 0.124

Gnomad EAS AF: 0.0226

Gnomad SAS AF: 0.0500

Gnomad FIN AF: 0.0993

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.109

Gnomad OTH AF: 0.120

GnomAD4 exome AF: 0.125 AC: 1 AN: 8 Hom.: 0 Cov.: 0 AF XY: 0.167 AC XY: 1 AN XY: 6

Gnomad4 FIN exome AF: 0.250

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.117 AC: 17852 AN: 151984 Hom.: 1159 Cov.: 32 AF XY: 0.115 AC XY: 8561 AN XY: 74252

Gnomad4 AFR AF: 0.163

Gnomad4 AMR AF: 0.101

Gnomad4 ASJ AF: 0.124

Gnomad4 EAS AF: 0.0227

Gnomad4 SAS AF: 0.0500

Gnomad4 FIN AF: 0.0993

Gnomad4 NFE AF: 0.109

Gnomad4 OTH AF: 0.118

Alfa AF: 0.108 Hom.: 1920

Bravo AF: 0.118

Asia WGS AF: 0.0540 AC: 192 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.0
DANN	Benign	0.32

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs16933090; hg19: chr11-16455794;