8-54458227-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_022454.4(SOX17):​c.89G>A​(p.Cys30Tyr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 34)

Consequence

SOX17
NM_022454.4 missense

Scores

4
7
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.53
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.3413856).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SOX17NM_022454.4 linkc.89G>A p.Cys30Tyr missense_variant 1/2 ENST00000297316.5 NP_071899.1 Q9H6I2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SOX17ENST00000297316.5 linkc.89G>A p.Cys30Tyr missense_variant 1/21 NM_022454.4 ENSP00000297316.4 Q9H6I2

Frequencies

GnomAD3 genomes
Cov.:
34
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
34

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Vesicoureteral reflux 3 Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingFulgent Genetics, Fulgent GeneticsJan 27, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.37
BayesDel_addAF
Pathogenic
0.21
D
BayesDel_noAF
Uncertain
0.060
CADD
Pathogenic
29
DANN
Uncertain
0.98
DEOGEN2
Uncertain
0.57
D
Eigen
Benign
-0.024
Eigen_PC
Benign
0.12
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Benign
0.60
T
M_CAP
Pathogenic
0.63
D
MetaRNN
Benign
0.34
T
MetaSVM
Uncertain
0.23
D
MutationAssessor
Benign
1.9
L
PrimateAI
Pathogenic
0.81
D
PROVEAN
Uncertain
-3.1
D
REVEL
Uncertain
0.60
Sift
Benign
0.88
T
Sift4G
Benign
0.45
T
Polyphen
0.25
B
Vest4
0.35
MutPred
0.31
Loss of catalytic residue at P29 (P = 0.0081);
MVP
0.60
MPC
2.4
ClinPred
0.97
D
GERP RS
4.2
Varity_R
0.36
gMVP
0.91

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-55370787; API