Variant 5-53484153-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_013409.3(FST):c.581G>A(p.Arg194Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00208 in 1,612,112 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0025 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0020 ( 11 hom. )

Consequence

FST
NM_013409.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 6.83

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.007940471).

BP6

Variant 5-53484153-G-A is Benign according to our data. Variant chr5-53484153-G-A is described in ClinVar as [Benign]. Clinvar id is 721052.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 378 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FST	NM_013409.3 linkuse as main transcript	c.581G>A	p.Arg194Gln	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 linkuse as main transcript	c.581G>A	p.Arg194Gln	missense_variant	4/6	1	NM_013409.3	ENSP00000256759	A1	P19883-1
FST	ENST00000396947.7 linkuse as main transcript	c.581G>A	p.Arg194Gln	missense_variant	4/6	5		ENSP00000380151	P4	P19883-2
FST	ENST00000504226.5 linkuse as main transcript	c.197G>A	p.Arg66Gln	missense_variant	2/4	3		ENSP00000426315
FST	ENST00000491717.1 linkuse as main transcript			downstream_gene_variant		2

Frequencies

GnomAD3 genomes

AF:

0.00249

AC:

379

AN:

152112

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000434

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00157

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.0190

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00169

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00290

AC:

730

AN:

251494

Hom.:

AF XY:

0.00299

AC XY:

407

AN XY:

135920

show subpopulations

Gnomad AFR exome

AF:

0.000308

Gnomad AMR exome

AF:

0.00113

Gnomad ASJ exome

AF:

0.00149

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.00206

Gnomad FIN exome

AF:

0.0184

Gnomad NFE exome

AF:

0.00171

Gnomad OTH exome

AF:

0.00212

GnomAD4 exome

AF:

0.00204

AC:

2981

AN:

1459882

Hom.:

Cov.:

AF XY:

0.00207

AC XY:

1503

AN XY:

726412

show subpopulations

Gnomad4 AFR exome

AF:

0.000299

Gnomad4 AMR exome

AF:

0.00107

Gnomad4 ASJ exome

AF:

0.00145

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00190

Gnomad4 FIN exome

AF:

0.0151

Gnomad4 NFE exome

AF:

0.00164

Gnomad4 OTH exome

AF:

0.00153

GnomAD4 genome

AF:

0.00248

AC:

378

AN:

152230

Hom.:

Cov.:

AF XY:

0.00320

AC XY:

238

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.000409

Gnomad4 AMR

AF:

0.00157

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.000387

Gnomad4 SAS

AF:

0.00124

Gnomad4 FIN

AF:

0.0190

Gnomad4 NFE

AF:

0.00169

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00165

Hom.:

Bravo

AF:

0.00123

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.00130

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00198

AC:

ExAC

AF:

0.00245

AC:

297

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00185

EpiControl

AF:

0.00124

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jul 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Uncertain

-0.050

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.38

T;.;T

Eigen

Pathogenic

0.70

Eigen_PC

Pathogenic

0.76

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.95

D;D;D

MetaRNN

Benign

0.0079

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.1

L;L;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.68

PROVEAN

Benign

-1.1

N;N;N

REVEL

Uncertain

0.35

Sift

Benign

0.13

T;T;T

Sift4G

Uncertain

0.025

D;T;D

Polyphen

1.0

D;.;.

Vest4

0.46

MVP

0.80

MPC

1.2

ClinPred

0.029

GERP RS

6.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.63

gMVP

0.76

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over