rs201101913

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_005634.3(SOX3):c.307C>A(p.Pro103Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00295 in 1,172,491 control chromosomes in the GnomAD database, including 44 homozygotes. There are 920 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.015 ( 17 hom., 459 hem., cov: 24)

Exomes 𝑓: 0.0017 ( 27 hom. 461 hem. )

Consequence

SOX3
NM_005634.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.274

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0020840764).

BP6

Variant X-140504754-G-T is Benign according to our data. Variant chrX-140504754-G-T is described in ClinVar as [Benign]. Clinvar id is 95302.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-140504754-G-T is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0151 (1707/112937) while in subpopulation AFR AF= 0.0504 (1571/31154). AF 95% confidence interval is 0.0484. There are 17 homozygotes in gnomad4. There are 459 alleles in male gnomad4 subpopulation. Median coverage is 24. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 17 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SOX3	NM_005634.3 link	c.307C>A	p.Pro103Thr	missense_variant	Exon 1 of 1	ENST00000370536.5	NP_005625.2	P41225

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SOX3	ENST00000370536.5 link	c.307C>A	p.Pro103Thr	missense_variant	Exon 1 of 1	6	NM_005634.3	ENSP00000359567.2		P41225

Frequencies

GnomAD3 genomes

AF:

0.0151

AC:

1707

AN:

112894

Hom.:

Cov.:

AF XY:

0.0130

AC XY:

457

AN XY:

35040

show subpopulations

Gnomad AFR

AF:

0.0505

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00870

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0126

Gnomad NFE

AF:

0.000357

Gnomad OTH

AF:

0.0137

GnomAD3 exomes

AF:

0.00484

AC:

577

AN:

119122

Hom.:

AF XY:

0.00387

AC XY:

113

AN XY:

29174

show subpopulations

Gnomad AFR exome

AF:

0.0566

Gnomad AMR exome

AF:

0.00338

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000182

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000295

Gnomad OTH exome

AF:

0.00259

GnomAD4 exome

AF:

0.00166

AC:

1754

AN:

1059554

Hom.:

Cov.:

AF XY:

0.00136

AC XY:

461

AN XY:

337754

show subpopulations

Gnomad4 AFR exome

AF:

0.0509

Gnomad4 AMR exome

AF:

0.00393

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000414

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000178

Gnomad4 OTH exome

AF:

0.00419

GnomAD4 genome

AF:

0.0151

AC:

1707

AN:

112937

Hom.:

Cov.:

AF XY:

0.0131

AC XY:

459

AN XY:

35093

show subpopulations

Gnomad4 AFR

AF:

0.0504

Gnomad4 AMR

AF:

0.00869

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000357

Gnomad4 OTH

AF:

0.0135

Alfa

AF:

0.00613

Hom.:

Bravo

AF:

0.0179

ESP6500AA

AF:

0.0453

AC:

168

ESP6500EA

AF:

0.000312

AC:

ExAC

AF:

0.00448

AC:

518

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Oct 31, 2013

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Nov 09, 2015

Ambry Genetics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

not provided

Benign:3

Jan 18, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Apr 13, 2015

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

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.063

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.66

CADD

Benign

DANN

Benign

0.92

DEOGEN2

Benign

0.30

FATHMM_MKL

Benign

0.70

LIST_S2

Benign

0.49

MetaRNN

Benign

0.0021

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.81

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

-1.8

REVEL

Benign

0.11

Sift

Benign

0.081

Sift4G

Benign

0.13

Polyphen

0.0

Vest4

0.062

MVP

0.21

ClinPred

0.0017

GERP RS

2.3

Varity_R

0.075

gMVP

0.64

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