dbSNP rs780362031: FSTL3:p.Arg2Ser (chr19-676427-C-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_005860.3(FSTL3):c.4C>A(p.Arg2Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000964 in 1,037,770 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R2C) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 9.6e-7 ( 0 hom. )

Consequence

FSTL3
NM_005860.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.233

Publications

0 publications found

Variant links:

Genes affected

FSTL3 (HGNC:3973): (follistatin like 3) Follistatin-like 3 is a secreted glycoprotein of the follistatin-module-protein family. It may have a role in leukemogenesis. [provided by RefSeq, Jul 2008]

FSTL3 links:

ENSG00000308766 (HGNC:):

ENSG00000308766 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3690923).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005860.3. 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
	FSTL3	NM_005860.3	MANE Select	c.4C>A	p.Arg2Ser	missense	Exon 1 of 5	NP_005851.1	O95633-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FSTL3	ENST00000166139.9	TSL:1 MANE Select	c.4C>A	p.Arg2Ser	missense	Exon 1 of 5	ENSP00000166139.3	O95633-1
FSTL3	ENST00000905299.1		c.4C>A	p.Arg2Ser	missense	Exon 1 of 4	ENSP00000575358.1
FSTL3	ENST00000964202.1		c.4C>A	p.Arg2Ser	missense	Exon 1 of 2	ENSP00000634261.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

9.64e-7

AC:

AN:

1037770

Hom.:

Cov.:

AF XY:

0.00000201

AC XY:

AN XY:

497610

show subpopulations

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

African (AFR)

AF:

0.00

AC:

AN:

21070

American (AMR)

AF:

0.00

AC:

AN:

9262

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

12416

East Asian (EAS)

AF:

0.0000429

AC:

AN:

23320

South Asian (SAS)

AF:

0.00

AC:

AN:

24548

European-Finnish (FIN)

AF:

0.00

AC:

AN:

20122

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2734

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

884360

Other (OTH)

AF:

0.00

AC:

AN:

39938

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.375

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.29

BayesDel_addAF

Benign

-0.10

BayesDel_noAF

Benign

-0.39

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.18

Eigen

Benign

-0.060

Eigen_PC

Benign

-0.15

FATHMM_MKL

Benign

0.46

LIST_S2

Benign

0.49

M_CAP

Uncertain

0.15

MetaRNN

Benign

0.37

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.8

PhyloP100

0.23

PrimateAI

Pathogenic

0.87

PROVEAN

Benign

-0.63

REVEL

Benign

0.12

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.032

Polyphen

0.96

Vest4

0.21

MutPred

0.20

Gain of glycosylation at R2 (P = 0.0037)

MVP

0.71

MPC

0.63

ClinPred

0.75

GERP RS

2.6

PromoterAI

0.21

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.25

gMVP

0.76

Mutation Taster

=81/19

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over