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):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• Tolchin-Le Caignec syndrome

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Illumina, G2P, Labcorp Genetics (formerly Invitae), PanelApp Australia, Ambry Genetics

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001367873.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SOX6	NM_001367873.1	MANE Select	c.1624-3579T>A		intron	N/A	NP_001354802.1	P35712-1
	SOX6	NM_001145819.2		c.1624-3579T>A		intron	N/A	NP_001139291.2	P35712-1
	SOX6	NM_033326.3		c.1624-3579T>A		intron	N/A	NP_201583.2	P35712-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SOX6	ENST00000683767.1	MANE Select	c.1624-3579T>A		intron	N/A	ENSP00000507545.1	P35712-1
	SOX6	ENST00000528429.5	TSL:1	c.1624-3579T>A		intron	N/A	ENSP00000433233.1	P35712-1
	SOX6	ENST00000396356.7	TSL:1	c.1624-3579T>A		intron	N/A	ENSP00000379644.3	P35712-3

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

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

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;