5-53482380-G-T

Variant names:

• chr5-53482380-G-T
• rs3756498
• NM_013409.3:c.86-500G>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_013409.3(FST):​c.86-500G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.00018 (0 hom., cov: 28)
  • Failed GnomAD Quality Control
• Consequence: FST NM_013409.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00200
• Publications: 10 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]

ENSG00000306075 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FST	NM_013409.3	c.86-500G>T		intron_variant	Intron 1 of 5	ENST00000256759.8	NP_037541.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FST	ENST00000256759.8	c.86-500G>T		intron_variant	Intron 1 of 5	1	NM_013409.3	ENSP00000256759.3
FST	ENST00000396947.7	c.86-500G>T		intron_variant	Intron 1 of 5	5		ENSP00000380151.2
ENSG00000306075	ENST00000815109.1	n.*82C>A		downstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.000180 AC: 24 AN: 133404 Hom.: 0 Cov.: 28

Gnomad AFR AF: 0.0000582

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000163

Gnomad ASJ AF: 0.000295

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000235

Gnomad FIN AF: 0.00105

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000125

Gnomad OTH AF: 0.00112

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000180 AC: 24 AN: 133476 Hom.: 0 Cov.: 28 AF XY: 0.000219 AC XY: 14 AN XY: 63828

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000580 AC: 2 AN: 34456

American (AMR) AF: 0.000163 AC: 2 AN: 12284

Ashkenazi Jewish (ASJ) AF: 0.000295 AC: 1 AN: 3386

East Asian (EAS) AF: 0.00 AC: 0 AN: 4600

South Asian (SAS) AF: 0.000236 AC: 1 AN: 4244

European-Finnish (FIN) AF: 0.00105 AC: 8 AN: 7586

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 234

European-Non Finnish (NFE) AF: 0.000125 AC: 8 AN: 64000

Other (OTH) AF: 0.00110 AC: 2 AN: 1812

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 8683

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.4
DANN	Benign	0.77
PhyloP100		-0.0020

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: rs3756498; hg19: chr5-52778210;