rs1127760
Positions:
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_013409.3(FST):c.715T>A(p.Cys239Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 12/21 in silico tools predict a damaging outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: not found (cov: 33)
Consequence
FST
NM_013409.3 missense
NM_013409.3 missense
Scores
13
5
1
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 7.92
Genes affected
FST (HGNC:3971): (follistatin) Follistatin is a single-chain gonadal protein that specifically inhibits follicle-stimulating hormone release. The single FST gene encodes two isoforms, FST317 and FST344 containing 317 and 344 amino acids respectively, resulting from alternative splicing of the precursor mRNA. In a study in which 37 candidate genes were tested for linkage and association with polycystic ovary syndrome (PCOS) or hyperandrogenemia in 150 families, evidence was found for linkage between PCOS and follistatin. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.988
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
FST | NM_013409.3 | c.715T>A | p.Cys239Ser | missense_variant | 4/6 | ENST00000256759.8 | NP_037541.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
FST | ENST00000256759.8 | c.715T>A | p.Cys239Ser | missense_variant | 4/6 | 1 | NM_013409.3 | ENSP00000256759.3 | ||
FST | ENST00000396947.7 | c.715T>A | p.Cys239Ser | missense_variant | 4/6 | 5 | ENSP00000380151.2 | |||
FST | ENST00000504226.5 | c.331T>A | p.Cys111Ser | missense_variant | 2/4 | 3 | ENSP00000426315.1 | |||
FST | ENST00000497789.2 | c.70T>A | p.Cys24Ser | missense_variant | 1/3 | 2 | ENSP00000426971.1 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 genomes
Cov.:
33
GnomAD4 exome Cov.: 30
GnomAD4 exome
Cov.:
30
GnomAD4 genome Cov.: 33
GnomAD4 genome
Cov.:
33
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Uncertain
D;.;T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;T
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D;D
MetaSVM
Pathogenic
D
MutationAssessor
Pathogenic
H;H;.
PrimateAI
Pathogenic
T
PROVEAN
Pathogenic
D;D;D
REVEL
Pathogenic
Sift
Pathogenic
D;D;D
Sift4G
Uncertain
D;D;D
Polyphen
D;.;.
Vest4
MutPred
Gain of disorder (P = 0.0056);Gain of disorder (P = 0.0056);.;
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at