NM_003108.4:c.67G>A

Variant names:

• chr2-5692788-G-A
• NM_003108.4:c.67G>A

Variant summary

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

The NM_003108.4(SOX11):​c.67G>A​(p.Glu23Lys) 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E23D) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SOX11 NM_003108.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.15
• Publications: 0 publications found

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]

SOX11 Gene-Disease associations (from GenCC):

• intellectual developmental disorder with microcephaly and with or without ocular malformations or hypogonadotropic hypogonadism

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae), PanelApp Australia
• Coffin-Siris syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

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=0.37162185).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003108.4. 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
	SOX11	NM_003108.4	MANE Select	c.67G>A	p.Glu23Lys	missense	Exon 1 of 1	NP_003099.1	P35716

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SOX11	ENST00000322002.5	TSL:6 MANE Select	c.67G>A	p.Glu23Lys	missense	Exon 1 of 1	ENSP00000322568.3	P35716

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

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	Pathogenic	0.81
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.020
CADD	Pathogenic	31
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.32	T
Eigen	Uncertain	0.29
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Uncertain	0.89	D
M_CAP	Pathogenic	0.81	D
MetaRNN	Benign	0.37	T
MetaSVM	Pathogenic	0.92	D
MutationAssessor	Benign	1.9	L
PhyloP100		5.1
PrimateAI	Pathogenic	0.95	D
PROVEAN	Benign	-1.5	N
REVEL	Uncertain	0.62
Sift	Uncertain	0.0030	D
Sift4G	Benign	0.13	T
Polyphen		0.86	P
Vest4		0.29
MutPred		0.34		Gain of ubiquitination at E23 (P = 0.0025)
MVP		0.94
MPC		2.1
ClinPred		0.95	D
GERP RS		3.1
PromoterAI		0.00090	Neutral
Varity_R		0.40
gMVP		0.95
Mutation Taster		=60/40	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: chr2-5832920; COSMIC: COSV58984082; COSMIC: COSV58984082;