2-5692784-G-T

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_003108.4(SOX11):c.63G>T(p.Thr21=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000996 in 1,612,168 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00062 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0010 (2 hom.)
• Consequence: SOX11 NM_003108.4 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.176

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 Benign. Variant got -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP6: Variant 2-5692784-G-T is Benign according to our data. Variant chr2-5692784-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 715893.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.176 with no splicing effect.
• BS2: High AC in GnomAd at 94 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SOX11	NM_003108.4	c.63G>T	p.Thr21=	synonymous_variant	1/1	ENST00000322002.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SOX11	ENST00000322002.5	c.63G>T	p.Thr21=	synonymous_variant	1/1		NM_003108.4	P1

Frequencies

GnomAD3 genomes AF: 0.000618 AC: 94 AN: 152198 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000169

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00122

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000453 AC: 112 AN: 247458 Hom.: 0 AF XY: 0.000447 AC XY: 60 AN XY: 134294

Gnomad AFR exome AF: 0.000127

Gnomad AMR exome AF: 0.0000875

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.000190

Gnomad NFE exome AF: 0.000913

Gnomad OTH exome AF: 0.000166

GnomAD4 exome AF: 0.00103 AC: 1511 AN: 1459970 Hom.: 2 Cov.: 33 AF XY: 0.000977 AC XY: 709 AN XY: 726012

Gnomad4 AFR exome AF: 0.0000598

Gnomad4 AMR exome AF: 0.0000672

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.000207

Gnomad4 NFE exome AF: 0.00132

Gnomad4 OTH exome AF: 0.000498

GnomAD4 genome AF: 0.000618 AC: 94 AN: 152198 Hom.: 0 Cov.: 32 AF XY: 0.000592 AC XY: 44 AN XY: 74356

Gnomad4 AFR AF: 0.000169

Gnomad4 AMR AF: 0.000196

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0000942

Gnomad4 NFE AF: 0.00122

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000914 Hom.: 0

Bravo AF: 0.000552

EpiCase AF: 0.000927

EpiControl AF: 0.000832

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Nov 01, 2023	SOX11: BP4, BP7 -
Likely benign, criteria provided, single submitter	clinical testing	Invitae	Jan 23, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
Cadd	Benign	11
Dann	Benign	0.95

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs139885563; hg19: chr2-5832916;