2-5693752-CCAGCAGCAGCGG-C

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP6BS2

The NM_003108.4(SOX11):c.1051_1062delAGCGGCAGCAGC(p.Ser351_Ser354del) variant causes a conservative inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000345 in 1,587,460 control chromosomes in the GnomAD database, including 2 homozygotes. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00058 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00032 ( 2 hom. )

Consequence

SOX11
NM_003108.4 conservative_inframe_deletion

Scores

Not classified

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2B:2

Conservation

PhyloP100: 1.61

Publications

1 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: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
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 -5 ACMG points.

BP6

Variant 2-5693752-CCAGCAGCAGCGG-C is Benign according to our data. Variant chr2-5693752-CCAGCAGCAGCGG-C is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 377015.

BS2

High AC in GnomAd4 at 88 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SOX11	NM_003108.4 link	c.1051_1062delAGCGGCAGCAGC	p.Ser351_Ser354del	conservative_inframe_deletion	Exon 1 of 1	ENST00000322002.5	NP_003099.1	P35716

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SOX11	ENST00000322002.5 link	c.1051_1062delAGCGGCAGCAGC	p.Ser351_Ser354del	conservative_inframe_deletion	Exon 1 of 1	6	NM_003108.4	ENSP00000322568.3		P35716

Frequencies

GnomAD3 genomes

AF:

0.000558

AC:

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00101

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000850

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.000827

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000323

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.000395

AC:

AN:

189906

AF XY:

0.000439

show subpopulations

Gnomad AFR exome

AF:

0.000390

Gnomad AMR exome

AF:

0.000960

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000267

Gnomad FIN exome

AF:

0.0000712

Gnomad NFE exome

AF:

0.000188

Gnomad OTH exome

AF:

0.000604

GnomAD4 exome

AF:

0.000320

AC:

459

AN:

1435148

Hom.:

AF XY:

0.000357

AC XY:

254

AN XY:

712024

show subpopulations

African (AFR)

AF:

0.000574

AC:

AN:

33088

American (AMR)

AF:

0.000957

AC:

AN:

41794

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25566

East Asian (EAS)

AF:

0.000129

AC:

AN:

38656

South Asian (SAS)

AF:

0.000875

AC:

AN:

83410

European-Finnish (FIN)

AF:

0.0000432

AC:

AN:

46328

Middle Eastern (MID)

AF:

0.00645

AC:

AN:

5732

European-Non Finnish (NFE)

AF:

0.000236

AC:

260

AN:

1101118

Other (OTH)

AF:

0.000387

AC:

AN:

59456

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.444

Heterozygous variant carriers

122

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<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

AF:

0.000578

AC:

AN:

152312

Hom.:

Cov.:

AF XY:

0.000645

AC XY:

AN XY:

74476

show subpopulations

African (AFR)

AF:

0.00106

AC:

AN:

41586

American (AMR)

AF:

0.000849

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.000194

AC:

AN:

5162

South Asian (SAS)

AF:

0.000828

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000323

AC:

AN:

68016

Other (OTH)

AF:

0.000473

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.0000397

Hom.:

Bravo

AF:

0.000480

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:2Benign:2

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Uncertain:1Benign:2

Nov 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

SOX11: BS1 -

Dec 07, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Aug 03, 2016

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Inborn genetic diseases

Uncertain:1

Feb 11, 2021

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.1051_1062del12 (p.S351_S354del) alteration is located in exon 1 (coding exon 1) of the SOX11 gene. This alteration consists of an in-frame deletion of 12 nucleotides between nucleotide positions c.1051 and c.1062, resulting in the deletion of 4 residues. This amino acid region is not well conserved in available vertebrate species. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.6

Mutation Taster

=111/89

polymorphism

(source)

Splicing

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over