Genetic Variant SOX17:p.Gly178Arg (chr8-54459282-G-C) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_022454.4(SOX17):c.532G>C(p.Gly178Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000331 in 1,508,598 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G178C) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000029 ( 0 hom. )

Consequence

SOX17
NM_022454.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.342

Publications

4 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: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.27225876).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SOX17	NM_022454.4 link	c.532G>C	p.Gly178Arg	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.532G>C	p.Gly178Arg	missense_variant	Exon 2 of 2	1	NM_022454.4	ENSP00000297316.4		Q9H6I2

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152148

Hom.:

Cov.:

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:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000101

AC:

AN:

99466

AF XY:

0.0000178

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000266

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000295

AC:

AN:

1356450

Hom.:

Cov.:

AF XY:

0.00000448

AC XY:

AN XY:

669062

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

27508

American (AMR)

AF:

0.00

AC:

AN:

30872

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23444

East Asian (EAS)

AF:

0.00

AC:

AN:

31628

South Asian (SAS)

AF:

0.00

AC:

AN:

75058

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40410

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5046

European-Non Finnish (NFE)

AF:

0.00000375

AC:

AN:

1066228

Other (OTH)

AF:

0.00

AC:

AN:

56256

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.538

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152148

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74320

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41454

American (AMR)

AF:

0.00

AC:

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5170

South Asian (SAS)

AF:

0.00

AC:

AN:

4838

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10604

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68008

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ExAC

AF:

0.0000105

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.46

BayesDel_addAF

Uncertain

0.050

BayesDel_noAF

Benign

-0.10

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.45

Eigen

Benign

-0.47

Eigen_PC

Benign

-0.56

FATHMM_MKL

Benign

0.38

LIST_S2

Benign

0.80

M_CAP

Pathogenic

0.89

MetaRNN

Benign

0.27

MetaSVM

Uncertain

0.71

MutationAssessor

Benign

1.0

PhyloP100

-0.34

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

-1.4

REVEL

Uncertain

0.46

Sift

Benign

0.035

Sift4G

Uncertain

0.014

Polyphen

0.93

Vest4

0.22

MutPred

0.34

Gain of solvent accessibility (P = 0.0456);

MVP

0.39

MPC

1.9

ClinPred

0.91

GERP RS

2.2

Varity_R

0.14

gMVP

0.31

Mutation Taster

=85/15

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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8-54459282-G-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over