chr5-53483680-G-C

Position:

• chr5-53483680-G-C

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The ENST00000256759.8(FST):​c.454G>C​(p.Glu152Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00551 in 1,614,152 control chromosomes in the GnomAD database, including 32 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.0043 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0056 (32 hom.)
• Consequence: FST ENST00000256759.8 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 9.76

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 Benign. Variant got -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0072375834).
• BP6: Variant 5-53483680-G-C is Benign according to our data. Variant chr5-53483680-G-C is described in ClinVar as [Benign]. Clinvar id is 719871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd4 at 649 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FST	NM_013409.3	c.454G>C	p.Glu152Gln	missense_variant	3/6	ENST00000256759.8	NP_037541.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FST	ENST00000256759.8	c.454G>C	p.Glu152Gln	missense_variant	3/6	1	NM_013409.3	ENSP00000256759	A1
FST	ENST00000396947.7	c.454G>C	p.Glu152Gln	missense_variant	3/6	5		ENSP00000380151	P4
FST	ENST00000504226.5	c.70G>C	p.Glu24Gln	missense_variant	1/4	3		ENSP00000426315
FST	ENST00000491717.1	n.555G>C		non_coding_transcript_exon_variant	2/3	2

Frequencies

GnomAD3 genomes AF: 0.00427 AC: 650 AN: 152188 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000651

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00209

Gnomad ASJ AF: 0.00518

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.0119

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.00633

Gnomad OTH AF: 0.00431

GnomAD3 exomes AF: 0.00440 AC: 1107 AN: 251438 Hom.: 3 AF XY: 0.00450 AC XY: 612 AN XY: 135902

Gnomad AFR exome AF: 0.000677

Gnomad AMR exome AF: 0.00139

Gnomad ASJ exome AF: 0.00407

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000588

Gnomad FIN exome AF: 0.0103

Gnomad NFE exome AF: 0.00648

Gnomad OTH exome AF: 0.00473

GnomAD4 exome AF: 0.00564 AC: 8242 AN: 1461846 Hom.: 32 Cov.: 33 AF XY: 0.00545 AC XY: 3965 AN XY: 727234

Gnomad4 AFR exome AF: 0.000508

Gnomad4 AMR exome AF: 0.00150

Gnomad4 ASJ exome AF: 0.00513

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.000556

Gnomad4 FIN exome AF: 0.0110

Gnomad4 NFE exome AF: 0.00633

Gnomad4 OTH exome AF: 0.00517

GnomAD4 genome AF: 0.00426 AC: 649 AN: 152306 Hom.: 0 Cov.: 32 AF XY: 0.00408 AC XY: 304 AN XY: 74468

Gnomad4 AFR AF: 0.000650

Gnomad4 AMR AF: 0.00209

Gnomad4 ASJ AF: 0.00518

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.0119

Gnomad4 NFE AF: 0.00634

Gnomad4 OTH AF: 0.00427

Alfa AF: 0.00533 Hom.: 1

Bravo AF: 0.00368

TwinsUK AF: 0.00431 AC: 16

ALSPAC AF: 0.00778 AC: 30

ESP6500AA AF: 0.00113 AC: 5

ESP6500EA AF: 0.00837 AC: 72

ExAC AF: 0.00443 AC: 538

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.00703

EpiControl AF: 0.00634

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 31, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.51	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.20	T;.;T
Eigen	Benign	0.049
Eigen_PC	Uncertain	0.28
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.78	T;T;D
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.0072	T;T;T
MetaSVM	Benign	-0.73	T
MutationAssessor	Benign	-0.47	N;N;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	0.13	N;N;N
REVEL	Benign	0.25
Sift	Benign	0.46	T;T;T
Sift4G	Benign	0.37	T;T;T
Polyphen		0.35	B;.;.
Vest4		0.29
MVP		0.51
MPC		1.1
ClinPred		0.058	T
GERP RS		5.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.41
gMVP		0.40

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

Other links and lift over

dbSNP: rs11745088; hg19: chr5-52779510;