11-15972819-C-T

Position:

• chr11-15972819-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2 PP2 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: Not reported in ClinVar
• Conservation: PhyloP100: 5.80

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant in gene, where missense usually causes diseases (based on misZ statistic), SOX6. . Gene score misZ 1.9285 (greater than the threshold 3.09). Trascript score misZ 3.2843 (greater than threshold 3.09). GenCC has associacion of gene with Tolchin-Le Caignec syndrome.
• BP4: Computational evidence support a benign effect (MetaRNN=0.28686178).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SOX6	NM_001367873.1	c.2477G>A	p.Ser826Asn	missense_variant	16/16	ENST00000683767.1	NP_001354802.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SOX6	ENST00000683767.1	c.2477G>A	p.Ser826Asn	missense_variant	16/16		NM_001367873.1	ENSP00000507545	A2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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;T;T;T
M_CAP	Benign	0.038	D
MetaRNN	Benign	0.29	T;T;T;T;T
MetaSVM	Pathogenic	0.90	D
MutationAssessor	Benign	1.9	.;.;.;.;M
MutationTaster	Benign	1.0	D;D;D;D;D;D
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-0.80	N;N;N;N;N
REVEL	Uncertain	0.45
Sift	Uncertain	0.0050	D;D;D;D;D
Sift4G	Benign	0.25	T;T;T;T;T
Polyphen		0.85	P;P;.;B;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

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-15994365;