rs587777480

Positions:

• chr2-5692899-T-C

Variant summary

Our verdict is Likely pathogenic. Variant got 9 ACMG points: 9P and 0B. PM1 PM2 PP3_Strong PP5

The NM_003108.4(SOX11):​c.178T>C​(p.Ser60Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SOX11 NM_003108.4 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 4.86

Genes affected

SOX11 (HGNC:11191): (SRY-box transcription factor 11) This intronless gene encodes a member of the SOX (SRY-related HMG-box) family of transcription factors involved in the regulation of embryonic development and in the determination of the cell fate. The encoded protein may act as a transcriptional regulator after forming a protein complex with other proteins. The protein may function in the developing nervous system and play a role in tumorigenesis. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_pathogenic. Variant got 9 ACMG points.

• PM1: In a helix (size 15) in uniprot entity SOX11_HUMAN there are 8 pathogenic changes around while only 0 benign (100%) in NM_003108.4
• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.981
• PP5: Variant 2-5692899-T-C is Pathogenic according to our data. Variant chr2-5692899-T-C is described in ClinVar as [Pathogenic]. Clinvar id is 139530.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr2-5692899-T-C is described in Lovd as [Likely_pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SOX11	NM_003108.4	c.178T>C	p.Ser60Pro	missense_variant	1/1	ENST00000322002.5	NP_003099.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SOX11	ENST00000322002.5	c.178T>C	p.Ser60Pro	missense_variant	1/1	6	NM_003108.4	ENSP00000322568.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Intellectual disability, autosomal dominant 27 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Jun 02, 2014

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.52	D
BayesDel_noAF	Pathogenic	0.51
CADD	Pathogenic	33
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.97	D
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.37
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.80	T
M_CAP	Pathogenic	0.97	D
MetaRNN	Pathogenic	0.98	D
MetaSVM	Pathogenic	1.1	D
MutationAssessor	Pathogenic	3.6	H
PrimateAI	Pathogenic	0.92	D
PROVEAN	Pathogenic	-4.5	D
REVEL	Pathogenic	0.97
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.60	P
Vest4		0.94
MutPred		0.81		Loss of MoRF binding (P = 0.0815);
MVP		1.0
MPC		2.4
ClinPred		0.99	D
GERP RS		3.1
Varity_R		0.99
gMVP		1.0

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

LitVar

Other links and lift over

dbSNP: rs587777480; hg19: chr2-5833031;