Genetic Variant SOX11:p.Ala5Glu (chr2-5692735-C-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_003108.4(SOX11):c.14C>A(p.Ala5Glu) variant causes a missense change. The variant allele was found at a frequency of 0.00000417 in 1,438,456 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000042 ( 1 hom. )

Consequence

SOX11
NM_003108.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.78

Publications

0 publications found

Variant links:

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

SOX11 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2

High AC in GnomAdExome4 at 6 AD gene.

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.14C>A	p.Ala5Glu	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.14C>A	p.Ala5Glu	missense	Exon 1 of 1	ENSP00000322568.3	P35716

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000867

AC:

AN:

230680

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000417

AC:

AN:

1438456

Hom.:

Cov.:

AF XY:

0.00000281

AC XY:

AN XY:

712002

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33202

American (AMR)

AF:

0.00

AC:

AN:

43798

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24634

East Asian (EAS)

AF:

0.0000254

AC:

AN:

39330

South Asian (SAS)

AF:

0.0000608

AC:

AN:

82296

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52094

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5674

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1098126

Other (OTH)

AF:

0.00

AC:

AN:

59302

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.32

BayesDel_addAF

Uncertain

0.13

BayesDel_noAF

Uncertain

-0.060

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.23

Eigen

Uncertain

0.39

Eigen_PC

Uncertain

0.34

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.73

M_CAP

Pathogenic

0.96

MetaRNN

Uncertain

0.48

MetaSVM

Pathogenic

0.95

MutationAssessor

Benign

1.8

PhyloP100

3.8

PrimateAI

Pathogenic

0.90

PROVEAN

Benign

-1.8

REVEL

Uncertain

0.39

Sift

Uncertain

0.0050

Sift4G

Uncertain

0.016

Polyphen

0.99

Vest4

0.28

MutPred

0.14

Gain of solvent accessibility (P = 0.154)

MVP

0.97

MPC

2.2

ClinPred

0.81

GERP RS

3.4

PromoterAI

0.033

Neutral

(source)

Varity_R

0.51

gMVP

0.93

Mutation Taster

=76/24

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over