5-53485767-A-T

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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 -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FST	NM_013409.3	c.953-184A>T		intron_variant	Intron 5 of 5	ENST00000256759.8	NP_037541.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FST	ENST00000256759.8	c.953-184A>T		intron_variant	Intron 5 of 5	1	NM_013409.3	ENSP00000256759.3
FST	ENST00000396947.7	c.*79A>T		3_prime_UTR_variant	Exon 6 of 6	5		ENSP00000380151.2
FST	ENST00000497789.2	c.*79A>T		3_prime_UTR_variant	Exon 3 of 3	2		ENSP00000426971.1
FST	ENST00000504226.5	c.566-184A>T		intron_variant	Intron 3 of 3	3		ENSP00000426315.1

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

Gnomad4 AFR exome AF: 0.752

Gnomad4 AMR exome AF: 0.619

Gnomad4 ASJ exome AF: 0.534

Gnomad4 EAS exome AF: 0.639

Gnomad4 SAS exome AF: 0.677

Gnomad4 FIN exome AF: 0.580

Gnomad4 NFE exome AF: 0.541

Gnomad4 OTH exome AF: 0.561

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

Gnomad4 AFR AF: 0.753

Gnomad4 AMR AF: 0.573

Gnomad4 ASJ AF: 0.543

Gnomad4 EAS AF: 0.653

Gnomad4 SAS AF: 0.679

Gnomad4 FIN AF: 0.580

Gnomad4 NFE AF: 0.547

Gnomad4 OTH AF: 0.573

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.0090
DANN	Benign	0.15

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

Publications

LitVar

Other links and lift over

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