chr11-15972819-C-T

Variant names:

• chr11-15972819-C-T
• NM_001367873.1:c.2477G>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001367873.1(SOX6):​c.2477G>A​(p.Ser826Asn) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SOX6 NM_001367873.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.80
• Publications: 0 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.28686178).

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.2477G>A	p.Ser826Asn	missense	Exon 16 of 16	NP_001354802.1	P35712-1
	SOX6	NM_001145819.2		c.2477G>A	p.Ser826Asn	missense	Exon 16 of 16	NP_001139291.2	P35712-1
	SOX6	NM_033326.3		c.2417G>A	p.Ser806Asn	missense	Exon 16 of 16	NP_201583.2	P35712-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SOX6	ENST00000683767.1	MANE Select	c.2477G>A	p.Ser826Asn	missense	Exon 16 of 16	ENSP00000507545.1	P35712-1
	SOX6	ENST00000528429.5	TSL:1	c.2477G>A	p.Ser826Asn	missense	Exon 16 of 16	ENSP00000433233.1	P35712-1
	SOX6	ENST00000396356.7	TSL:1	c.2417G>A	p.Ser806Asn	missense	Exon 16 of 16	ENSP00000379644.3	P35712-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.26	T
Eigen	Uncertain	0.39
Eigen_PC	Uncertain	0.53
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.85	T
M_CAP	Benign	0.038	D
MetaRNN	Benign	0.29	T
MetaSVM	Pathogenic	0.90	D
MutationAssessor	Benign	1.9	M
PhyloP100		5.8
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-0.80	N
REVEL	Uncertain	0.45
Sift	Uncertain	0.0050	D
Sift4G	Benign	0.25	T
Polyphen		0.85	P
Vest4		0.31
MutPred		0.086		Loss of phosphorylation at S826 (P = 0.0075)
MVP		0.80
MPC		1.2
ClinPred		0.66	D
GERP RS		6.1
Varity_R		0.35
gMVP		0.35
Mutation Taster		=71/29	polymorphism

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

hg19: chr11-15994365;