rs773779294

Variant names:

• chr5-53480808-A-C
• rs773779294
• NM_013409.3:c.17A>C

Your query was ambiguous. Multiple possible variants found:

• chr5-53480808-A-C
• chr5-53480808-A-G

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_013409.3(FST):​c.17A>C​(p.His6Pro) variant causes a missense change. The variant allele was found at a frequency of 0.0000152 in 1,516,834 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H6Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 29)
  • Exomes 𝑓: 0.000015 (0 hom.)
• Consequence: FST NM_013409.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.98
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.07575151).
• BS2: High AC in GnomAdExome4 at 21 AD gene.

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.17A>C	p.His6Pro	missense	Exon 1 of 6	NP_037541.1	P19883-1
	FST	NM_006350.5		c.17A>C	p.His6Pro	missense	Exon 1 of 6	NP_006341.1	P19883-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FST	ENST00000256759.8	TSL:1 MANE Select	c.17A>C	p.His6Pro	missense	Exon 1 of 6	ENSP00000256759.3	P19883-1
	FST	ENST00000901914.1		c.17A>C	p.His6Pro	missense	Exon 1 of 6	ENSP00000571973.1
	FST	ENST00000918518.1		c.17A>C	p.His6Pro	missense	Exon 1 of 6	ENSP00000588577.1

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 151716 Hom.: 0 Cov.: 29

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000656

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000112 AC: 14 AN: 125378 AF XY: 0.000104

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000475

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00113

GnomAD4 exome AF: 0.0000154 AC: 21 AN: 1365118 Hom.: 0 Cov.: 27 AF XY: 0.0000163 AC XY: 11 AN XY: 673326

African (AFR) AF: 0.00 AC: 0 AN: 29372

American (AMR) AF: 0.000397 AC: 13 AN: 32768

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24392

East Asian (EAS) AF: 0.00 AC: 0 AN: 32612

South Asian (SAS) AF: 0.00 AC: 0 AN: 76018

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47164

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4804

European-Non Finnish (NFE) AF: 0.00000754 AC: 8 AN: 1061566

Other (OTH) AF: 0.00 AC: 0 AN: 56422

GnomAD4 genome AF: 0.0000132 AC: 2 AN: 151716 Hom.: 0 Cov.: 29 AF XY: 0.0000270 AC XY: 2 AN XY: 74086

African (AFR) AF: 0.00 AC: 0 AN: 41396

American (AMR) AF: 0.0000656 AC: 1 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5152

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10428

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67906

Other (OTH) AF: 0.00 AC: 0 AN: 2080

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.000117

ExAC AF: 0.0000196 AC: 1

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.047
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	20
DANN	Benign	0.86
DEOGEN2	Benign	0.35	T
Eigen	Benign	-0.45
Eigen_PC	Benign	-0.31
FATHMM_MKL	Benign	0.72	D
LIST_S2	Benign	0.67	T
M_CAP	Benign	0.0058	T
MetaRNN	Benign	0.076	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.69	N
PhyloP100		4.0
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-0.75	N
REVEL	Benign	0.099
Sift	Benign	0.11	T
Sift4G	Benign	0.11	T
Polyphen		0.044	B
Vest4		0.13
MutPred		0.36		Gain of catalytic residue at H6 (P = 0.0198)
MVP		0.62
MPC		1.4
ClinPred		0.026	T
GERP RS		3.3
PromoterAI		0.11	Neutral
Varity_R		0.18
gMVP		0.74
Mutation Taster		=71/29	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs773779294; hg19: chr5-52776638;