chr5-53485767-A-T

Variant names:

• chr5-53485767-A-T
• rs722910
• NM_013409.3:c.953-184A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006350.5(FST):​c.*79A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.565 in 1,581,014 control chromosomes in the GnomAD database, including 255,355 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.62 (29305 hom., cov: 29)
  • Exomes 𝑓: 0.56 (226050 hom.)
• Consequence: FST NM_006350.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.70
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.746 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006350.5. 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.953-184A>T		intron	N/A	NP_037541.1	P19883-1
	FST	NM_006350.5		c.*79A>T		3_prime_UTR	Exon 6 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.953-184A>T		intron	N/A	ENSP00000256759.3	P19883-1
	FST	ENST00000396947.7	TSL:5	c.*79A>T		3_prime_UTR	Exon 6 of 6	ENSP00000380151.2	P19883-2
	FST	ENST00000497789.2	TSL:2	c.*79A>T		3_prime_UTR	Exon 3 of 3	ENSP00000426971.1	H0YAF9

Frequencies

GnomAD3 genomes AF: 0.615 AC: 93198 AN: 151542 Hom.: 29260 Cov.: 29

Gnomad AFR AF: 0.753

Gnomad AMI AF: 0.417

Gnomad AMR AF: 0.572

Gnomad ASJ AF: 0.543

Gnomad EAS AF: 0.653

Gnomad SAS AF: 0.677

Gnomad FIN AF: 0.580

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.547

Gnomad OTH AF: 0.572

GnomAD4 exome AF: 0.560 AC: 800264 AN: 1429354 Hom.: 226050 Cov.: 30 AF XY: 0.562 AC XY: 399525 AN XY: 711262

African (AFR) AF: 0.752 AC: 23522 AN: 31298

American (AMR) AF: 0.619 AC: 23039 AN: 37234

Ashkenazi Jewish (ASJ) AF: 0.534 AC: 13388 AN: 25050

East Asian (EAS) AF: 0.639 AC: 25262 AN: 39544

South Asian (SAS) AF: 0.677 AC: 54813 AN: 81004

European-Finnish (FIN) AF: 0.580 AC: 30811 AN: 53112

Middle Eastern (MID) AF: 0.495 AC: 2787 AN: 5626

European-Non Finnish (NFE) AF: 0.541 AC: 593511 AN: 1097394

Other (OTH) AF: 0.561 AC: 33131 AN: 59092

GnomAD4 genome AF: 0.615 AC: 93299 AN: 151660 Hom.: 29305 Cov.: 29 AF XY: 0.617 AC XY: 45701 AN XY: 74116

African (AFR) AF: 0.753 AC: 31152 AN: 41356

American (AMR) AF: 0.573 AC: 8727 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.543 AC: 1882 AN: 3464

East Asian (EAS) AF: 0.653 AC: 3360 AN: 5144

South Asian (SAS) AF: 0.679 AC: 3260 AN: 4804

European-Finnish (FIN) AF: 0.580 AC: 6061 AN: 10458

Middle Eastern (MID) AF: 0.476 AC: 140 AN: 294

European-Non Finnish (NFE) AF: 0.547 AC: 37135 AN: 67894

Other (OTH) AF: 0.573 AC: 1203 AN: 2100

Alfa AF: 0.403 Hom.: 802

Bravo AF: 0.618

Asia WGS AF: 0.652 AC: 2267 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.0090
DANN	Benign	0.15
PhyloP100		-1.7
Mutation Taster		=21/79	disease causing

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: rs722910; hg19: chr5-52781597; COSMIC: COSV56814907; COSMIC: COSV56814907;