Variant X-140504115-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_005634.3(SOX3):c.946G>A(p.Gly316Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000889 in 1,023,154 control chromosomes in the GnomAD database, including 1 homozygotes. There are 28 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00020 ( 0 hom., 5 hem., cov: 23)

Exomes 𝑓: 0.000076 ( 1 hom. 23 hem. )

Consequence

SOX3
NM_005634.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: 1.51

Variant links:

Genes affected

SOX3 (HGNC:11199): (SRY-box transcription factor 3) This 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. Mutations in this gene have been associated with X-linked cognitive disability with growth hormone deficiency. [provided by RefSeq, Jul 2008]

SOX3 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.006720066).

BP6

Variant X-140504115-C-T is Benign according to our data. Variant chrX-140504115-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2042516.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAd4 at 5 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SOX3	NM_005634.3 linkuse as main transcript	c.946G>A	p.Gly316Ser	missense_variant	1/1	ENST00000370536.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SOX3	ENST00000370536.5 linkuse as main transcript	c.946G>A	p.Gly316Ser	missense_variant	1/1		NM_005634.3	P1

Frequencies

GnomAD3 genomes

AF:

0.000196

AC:

AN:

107158

Hom.:

Cov.:

AF XY:

0.000160

AC XY:

AN XY:

31300

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00542

Gnomad SAS

AF:

0.000788

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000700

GnomAD3 exomes

AF:

0.000139

AC:

AN:

28808

Hom.:

AF XY:

0.00

AC XY:

AN XY:

5610

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00285

Gnomad SAS exome

AF:

0.000257

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000764

AC:

AN:

915956

Hom.:

Cov.:

AF XY:

0.0000803

AC XY:

AN XY:

286470

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00141

Gnomad4 SAS exome

AF:

0.000201

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000133

Gnomad4 OTH exome

AF:

0.000874

GnomAD4 genome

AF:

0.000196

AC:

AN:

107198

Hom.:

Cov.:

AF XY:

0.000160

AC XY:

AN XY:

31346

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00543

Gnomad4 SAS

AF:

0.000793

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000690

Alfa

AF:

0.000190

Hom.:

Bravo

AF:

0.000193

ExAC

AF:

0.0000755

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Sep 12, 2023

- -

SOX3-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 18, 2023

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.086

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Benign

0.63

DEOGEN2

Benign

0.22

FATHMM_MKL

Benign

0.098

LIST_S2

Benign

0.57

M_CAP

Pathogenic

0.38

MetaRNN

Benign

0.0067

MetaSVM

Benign

-0.80

MutationAssessor

Benign

0.34

MutationTaster

Benign

1.0

PrimateAI

Pathogenic

0.94

PROVEAN

Benign

0.25

REVEL

Benign

0.16

Sift

Benign

0.78

Sift4G

Benign

0.82

Polyphen

0.38

Vest4

0.067

MutPred

0.15

Gain of glycosylation at G316 (P = 0.013);

MVP

0.27

ClinPred

0.031

GERP RS

2.9

Varity_R

0.10

gMVP

0.36

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over