5-53485117-A-G

Position:

• chr5-53485117-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_013409.3(FST):​c.842A>G​(p.Glu281Gly) 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 benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: FST NM_013409.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.87

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]

ACMG classification

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=0.42017007).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FST	NM_013409.3	c.842A>G	p.Glu281Gly	missense_variant	5/6	ENST00000256759.8	NP_037541.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FST	ENST00000256759.8	c.842A>G	p.Glu281Gly	missense_variant	5/6	1	NM_013409.3	ENSP00000256759	A1
FST	ENST00000396947.7	c.842A>G	p.Glu281Gly	missense_variant	5/6	5		ENSP00000380151	P4
FST	ENST00000504226.5	c.455A>G	p.Glu152Gly	missense_variant	3/4	3		ENSP00000426315
FST	ENST00000497789.2	c.197A>G	p.Glu66Gly	missense_variant	2/3	2		ENSP00000426971

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 14, 2023

The c.842A>G (p.E281G) alteration is located in exon 5 (coding exon 5) of the FST gene. This alteration results from a A to G substitution at nucleotide position 842, causing the glutamic acid (E) at amino acid position 281 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Uncertain	0.088	D
BayesDel_noAF	Benign	-0.11
CADD	Pathogenic	30
DANN	Uncertain	1.0
DEOGEN2	Benign	0.28	T;.;T
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.97	D;D;D
M_CAP	Benign	0.035	D
MetaRNN	Benign	0.42	T;T;T
MetaSVM	Benign	-0.59	T
MutationAssessor	Benign	0.95	L;L;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-1.2	N;N;N
REVEL	Benign	0.22
Sift	Benign	0.18	T;T;T
Sift4G	Uncertain	0.0050	D;D;D
Polyphen		0.87	P;.;.
Vest4		0.75
MutPred		0.39		Loss of sheet (P = 0.0457);Loss of sheet (P = 0.0457);.;
MVP		0.70
MPC		1.8
ClinPred		0.83	D
GERP RS		5.5
Varity_R		0.34
gMVP		0.95

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-52780947;