dbSNP rs1554579184: SOX17:p.Glu152Asp (chr8-54459206-G-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate

The NM_022454.4(SOX17):c.456G>C(p.Glu152Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000699 in 1,429,652 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

SOX17
NM_022454.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.00100

Publications

0 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, STRONG Submitted by: ClinGen, PanelApp Australia
vesicoureteral reflux 3
Inheritance: AD Classification: DEFINITIVE, STRONG, LIMITED Submitted by: G2P, Ambry Genetics, PanelApp Australia, 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: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.16301778).

BP6

Variant 8-54459206-G-C is Benign according to our data. Variant chr8-54459206-G-C is described in ClinVar as Likely_benign. ClinVar VariationId is 523052.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022454.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SOX17	NM_022454.4	MANE Select	c.456G>C	p.Glu152Asp	missense	Exon 2 of 2	NP_071899.1	Q9H6I2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SOX17	ENST00000297316.5	TSL:1 MANE Select	c.456G>C	p.Glu152Asp	missense	Exon 2 of 2	ENSP00000297316.4	Q9H6I2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.99e-7

AC:

AN:

1429652

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

709546

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30810

American (AMR)

AF:

0.00

AC:

AN:

40816

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25132

East Asian (EAS)

AF:

0.00

AC:

AN:

36880

South Asian (SAS)

AF:

0.00

AC:

AN:

82628

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50236

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5656

European-Non Finnish (NFE)

AF:

9.10e-7

AC:

AN:

1098394

Other (OTH)

AF:

0.00

AC:

AN:

59100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Vesicoureteral reflux (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.056

BayesDel_noAF

Benign

-0.32

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.38

Eigen

Benign

-0.63

Eigen_PC

Benign

-0.54

FATHMM_MKL

Benign

0.34

LIST_S2

Benign

0.78

M_CAP

Pathogenic

0.69

MetaRNN

Benign

0.16

MetaSVM

Uncertain

0.27

MutationAssessor

Benign

1.1

PhyloP100

0.0010

PrimateAI

Uncertain

0.79

PROVEAN

Benign

-0.54

REVEL

Benign

0.29

Sift

Benign

0.40

Sift4G

Benign

0.44

Polyphen

0.12

Vest4

0.061

MutPred

0.24

Loss of methylation at K149 (P = 0.1183)

MVP

0.39

MPC

1.7

ClinPred

0.38

GERP RS

3.0

Varity_R

0.17

gMVP

0.15

Mutation Taster

=88/12

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over