rs267607083

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_022454.4(SOX17):c.775T>A(p.Tyr259Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00234 in 1,529,242 control chromosomes in the GnomAD database, including 20 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0025 ( 2 hom., cov: 33)

Exomes 𝑓: 0.0023 ( 18 hom. )

Consequence

SOX17
NM_022454.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts U:1B:6

Conservation

PhyloP100: 1.74

Publications

9 publications found

Variant links:

Genes affected

SOX17 (HGNC:18122): (SRY-box transcription factor 17) 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. [provided by RefSeq, Jul 2008]

SOX17 Gene-Disease associations (from GenCC):

pulmonary arterial hypertension
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
vesicoureteral reflux 3
Inheritance: AD Classification: DEFINITIVE, STRONG, LIMITED Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
familial vesicoureteral reflux
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

SOX17 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0069889724).

BP6

Variant 8-54459525-T-A is Benign according to our data. Variant chr8-54459525-T-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 18413.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 387 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SOX17	NM_022454.4 link	c.775T>A	p.Tyr259Asn	missense_variant	Exon 2 of 2	ENST00000297316.5	NP_071899.1	Q9H6I2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SOX17	ENST00000297316.5 link	c.775T>A	p.Tyr259Asn	missense_variant	Exon 2 of 2	1	NM_022454.4	ENSP00000297316.4		Q9H6I2

Frequencies

GnomAD3 genomes

AF:

0.00255

AC:

388

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000603

Gnomad AMI

AF:

0.00329

Gnomad AMR

AF:

0.00660

Gnomad ASJ

AF:

0.0173

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00806

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.0350

Gnomad NFE

AF:

0.00196

Gnomad OTH

AF:

0.00669

GnomAD2 exomes

AF:

0.00380

AC:

467

AN:

122834

AF XY:

0.00403

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00406

Gnomad ASJ exome

AF:

0.0101

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000374

Gnomad NFE exome

AF:

0.00205

Gnomad OTH exome

AF:

0.00525

GnomAD4 exome

AF:

0.00232

AC:

3192

AN:

1376940

Hom.:

Cov.:

AF XY:

0.00252

AC XY:

1713

AN XY:

679150

show subpopulations

African (AFR)

AF:

0.000326

AC:

AN:

30718

American (AMR)

AF:

0.00415

AC:

147

AN:

35398

Ashkenazi Jewish (ASJ)

AF:

0.0109

AC:

271

AN:

24940

East Asian (EAS)

AF:

0.00

AC:

AN:

35058

South Asian (SAS)

AF:

0.00684

AC:

538

AN:

78672

European-Finnish (FIN)

AF:

0.000149

AC:

AN:

33502

Middle Eastern (MID)

AF:

0.0161

AC:

AN:

4670

European-Non Finnish (NFE)

AF:

0.00181

AC:

1944

AN:

1076474

Other (OTH)

AF:

0.00351

AC:

202

AN:

57508

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

221

442

664

885

1106

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

148

222

296

370

<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:

0.00254

AC:

387

AN:

152302

Hom.:

Cov.:

AF XY:

0.00286

AC XY:

213

AN XY:

74472

show subpopulations

African (AFR)

AF:

0.000601

AC:

AN:

41572

American (AMR)

AF:

0.00660

AC:

101

AN:

15312

Ashkenazi Jewish (ASJ)

AF:

0.0173

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5164

South Asian (SAS)

AF:

0.00807

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.000188

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.0342

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00196

AC:

133

AN:

68002

Other (OTH)

AF:

0.00662

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

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:

0.00313

Hom.:

Bravo

AF:

0.00253

ExAC

AF:

0.00147

AC:

118

Asia WGS

AF:

0.00290

AC:

AN:

3468

ClinVar

Significance: Benign/Likely benign

Submissions summary: Uncertain:1Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Jan 23, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Mar 05, 2025

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

See Variant Classification Assertion Criteria. -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

May 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

SOX17: BS2 -

Vesicoureteral reflux 3

Uncertain:1Benign:1

May 28, 2019

Mendelics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Dec 01, 2010

OMIM

Significance:Uncertain significance

Review Status:no assertion criteria provided

Collection Method:literature only

- -

SOX17-related disorder

Benign:1

Jun 28, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as 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

0.25

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.24

CADD

Uncertain

(source)

DANN

Uncertain

0.98

DEOGEN2

Uncertain

0.49

Eigen

Benign

0.13

Eigen_PC

Benign

0.044

FATHMM_MKL

Benign

0.17

LIST_S2

Benign

0.66

MetaRNN

Benign

0.0070

MetaSVM

Benign

-0.57

MutationAssessor

Uncertain

2.5

PhyloP100

1.7

PrimateAI

Pathogenic

0.87

PROVEAN

Benign

-2.3

REVEL

Uncertain

0.32

Sift

Benign

0.065

Sift4G

Benign

0.15

Polyphen

0.95

Vest4

0.77

MVP

0.68

MPC

2.4

ClinPred

0.058

GERP RS

4.2

Varity_R

0.19

gMVP

0.48

Mutation Taster

=98/2

polymorphism

(source)

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

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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