rs16932455

Variant names:

• chr11-16018629-A-T
• rs16932455
• NM_001367873.1:c.1624-3579T>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BA1

The NM_001367873.1(SOX6):​c.1624-3579T>A variant causes a intron change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0742 in 152,108 control chromosomes in the GnomAD database, including 858 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.074 (858 hom., cov: 32)
• Consequence: SOX6 NM_001367873.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 8.55
• 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=-0.24).
• BP6: Variant 11-16018629-A-T is Benign according to our data. Variant chr11-16018629-A-T is described in ClinVar as Benign. ClinVar VariationId is 1286591.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.341 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SOX6	NM_001367873.1	c.1624-3579T>A		intron_variant	Intron 12 of 15	ENST00000683767.1	NP_001354802.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SOX6	ENST00000683767.1	c.1624-3579T>A		intron_variant	Intron 12 of 15		NM_001367873.1	ENSP00000507545.1

Frequencies

GnomAD3 genomes AF: 0.0742 AC: 11282 AN: 151988 Hom.: 857 Cov.: 32

Gnomad AFR AF: 0.135

Gnomad AMI AF: 0.0252

Gnomad AMR AF: 0.117

Gnomad ASJ AF: 0.0557

Gnomad EAS AF: 0.355

Gnomad SAS AF: 0.0458

Gnomad FIN AF: 0.0850

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.00901

Gnomad OTH AF: 0.0627

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

GnomAD4 genome AF: 0.0742 AC: 11290 AN: 152108 Hom.: 858 Cov.: 32 AF XY: 0.0787 AC XY: 5852 AN XY: 74348

African (AFR) AF: 0.135 AC: 5591 AN: 41498

American (AMR) AF: 0.117 AC: 1788 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.0557 AC: 193 AN: 3466

East Asian (EAS) AF: 0.355 AC: 1824 AN: 5142

South Asian (SAS) AF: 0.0448 AC: 216 AN: 4822

European-Finnish (FIN) AF: 0.0850 AC: 900 AN: 10592

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.00901 AC: 613 AN: 68006

Other (OTH) AF: 0.0625 AC: 132 AN: 2112

Alfa AF: 0.0468 Hom.: 54

Bravo AF: 0.0862

Asia WGS AF: 0.197 AC: 679 AN: 3464

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Nov 02, 2020

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 29518216) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.24
CADD	Benign	22
DANN	Benign	0.78
PhyloP100		8.5
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: rs16932455; hg19: chr11-16040175;