rs751221446

chr2-5693752-CCAGCAGCAGCGG-Cchr2-5693752-CCAGCAGCAGCGG-CCAGCAGCAGCGGCAGCAGCAGCGG

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP6 BS2

The NM_003108.4(SOX11):c.1051_1062del(p.Ser351_Ser354del) variant causes a 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. 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 inframe_deletion
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2 B:2
• Conservation: PhyloP100: 1.61

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_benign. Variant got -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 id is 377015.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=2, Uncertain_significance=2}. Variant chr2-5693752-CCAGCAGCAGCGG-C is described in Lovd as [Likely_benign].
• BS2: High AC in GnomAd at 85 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SOX11	NM_003108.4	c.1051_1062del	p.Ser351_Ser354del	inframe_deletion	1/1	ENST00000322002.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SOX11	ENST00000322002.5	c.1051_1062del	p.Ser351_Ser354del	inframe_deletion	1/1		NM_003108.4	P1

Frequencies

GnomAD3 genomes AF: 0.000558 AC: 85 AN: 152196 Hom.: 0 Cov.: 32

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

GnomAD3 exomes AF: 0.000395 AC: 75 AN: 189906 Hom.: 0 AF XY: 0.000439 AC XY: 46 AN XY: 104748

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 SAS exome AF: 0.000709

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.: 2 AF XY: 0.000357 AC XY: 254 AN XY: 712024

Gnomad4 AFR exome AF: 0.000574

Gnomad4 AMR exome AF: 0.000957

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000129

Gnomad4 SAS exome AF: 0.000875

Gnomad4 FIN exome AF: 0.0000432

Gnomad4 NFE exome AF: 0.000236

Gnomad4 OTH exome AF: 0.000387

GnomAD4 genome AF: 0.000578 AC: 88 AN: 152312 Hom.: 0 Cov.: 32 AF XY: 0.000645 AC XY: 48 AN XY: 74476

Gnomad4 AFR AF: 0.00106

Gnomad4 AMR AF: 0.000849

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000194

Gnomad4 SAS AF: 0.000828

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000323

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.0000397 Hom.: 0

Bravo AF: 0.000480

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:2 Benign:2

Revision: criteria provided, conflicting classifications

Submissions by phenotype

not provided Uncertain:1 Benign:2

Uncertain significance, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Aug 03, 2016	- -
Likely benign, criteria provided, single submitter	clinical testing	Invitae	Dec 25, 2023	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Nov 01, 2023	SOX11: BS1 -

Inborn genetic diseases Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 11, 2021

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

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs751221446; hg19: chr2-5833884;