5-53483680-G-C

Variant names:

• chr5-53483680-G-C
• rs11745088
• NM_013409.3:c.454G>C

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_013409.3(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. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0043 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0056 (32 hom.)
• Consequence: FST NM_013409.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 9.76
• Publications: 13 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: Benign. The variant received -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 VariationId is 719871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd4 at 649 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.454G>C	p.Glu152Gln	missense	Exon 3 of 6	NP_037541.1	P19883-1
	FST	NM_006350.5		c.454G>C	p.Glu152Gln	missense	Exon 3 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.454G>C	p.Glu152Gln	missense	Exon 3 of 6	ENSP00000256759.3	P19883-1
	FST	ENST00000901914.1		c.454G>C	p.Glu152Gln	missense	Exon 3 of 6	ENSP00000571973.1
	FST	ENST00000918518.1		c.454G>C	p.Glu152Gln	missense	Exon 3 of 6	ENSP00000588577.1

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

GnomAD2 exomes AF: 0.00440 AC: 1107 AN: 251438 AF XY: 0.00450

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 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

African (AFR) AF: 0.000508 AC: 17 AN: 33480

American (AMR) AF: 0.00150 AC: 67 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00513 AC: 134 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.000556 AC: 48 AN: 86258

European-Finnish (FIN) AF: 0.0110 AC: 587 AN: 53420

Middle Eastern (MID) AF: 0.00607 AC: 35 AN: 5768

European-Non Finnish (NFE) AF: 0.00633 AC: 7041 AN: 1111970

Other (OTH) AF: 0.00517 AC: 312 AN: 60392

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

African (AFR) AF: 0.000650 AC: 27 AN: 41568

American (AMR) AF: 0.00209 AC: 32 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00518 AC: 18 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5184

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4820

European-Finnish (FIN) AF: 0.0119 AC: 126 AN: 10610

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.00634 AC: 431 AN: 68034

Other (OTH) AF: 0.00427 AC: 9 AN: 2110

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

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

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
Eigen	Benign	0.049
Eigen_PC	Uncertain	0.28
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.0072	T
MetaSVM	Benign	-0.73	T
MutationAssessor	Benign	-0.47	N
PhyloP100		9.8
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	0.13	N
REVEL	Benign	0.25
Sift	Benign	0.46	T
Sift4G	Benign	0.37	T
Polyphen		0.35	B
Vest4		0.29
MVP		0.51
MPC		1.1
ClinPred		0.058	T
GERP RS		5.8
PromoterAI		0.059	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.41
gMVP		0.40
Mutation Taster		=86/14	polymorphism

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

Other links and lift over

dbSNP: rs11745088; hg19: chr5-52779510;