dbSNP rs1062809: FST:p.Ser230Tyr (chr5-53484261-C-A) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_013409.3(FST):c.689C>A(p.Ser230Tyr) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

FST
NM_013409.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.83

Publications

4 publications found

Variant links:

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]

FST links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.798

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013409.3. 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
	FST	NM_013409.3	MANE Select	c.689C>A	p.Ser230Tyr	missense	Exon 4 of 6	NP_037541.1	P19883-1
	FST	NM_006350.5		c.689C>A	p.Ser230Tyr	missense	Exon 4 of 6	NP_006341.1	P19883-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FST	ENST00000256759.8	TSL:1 MANE Select	c.689C>A	p.Ser230Tyr	missense	Exon 4 of 6	ENSP00000256759.3	P19883-1
FST	ENST00000901914.1		c.689C>A	p.Ser230Tyr	missense	Exon 4 of 6	ENSP00000571973.1
FST	ENST00000918518.1		c.689C>A	p.Ser230Tyr	missense	Exon 4 of 6	ENSP00000588577.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1458860

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726010

African (AFR)

AF:

0.00

AC:

AN:

33416

American (AMR)

AF:

0.00

AC:

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26122

East Asian (EAS)

AF:

0.00

AC:

AN:

39682

South Asian (SAS)

AF:

0.00

AC:

AN:

86218

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1109220

Other (OTH)

AF:

0.00

AC:

AN:

60298

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.96

BayesDel_addAF

Uncertain

0.10

BayesDel_noAF

Benign

-0.090

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.41

Eigen

Pathogenic

0.96

Eigen_PC

Pathogenic

0.95

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.96

M_CAP

Benign

0.028

MetaRNN

Pathogenic

0.80

MetaSVM

Benign

-1.2

MutationAssessor

Uncertain

2.5

PhyloP100

7.8

PrimateAI

Pathogenic

0.81

PROVEAN

Pathogenic

-4.7

REVEL

Uncertain

0.47

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0020

Polyphen

1.0

Vest4

0.92

MutPred

0.59

Loss of MoRF binding (P = 0.2248)

MVP

0.67

MPC

2.4

ClinPred

0.99

GERP RS

6.2

PromoterAI

0.0019

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.76

gMVP

0.82

Mutation Taster

=24/76

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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