Genetic Variant FSTL3:p.Arg166Cys (chr19-680480-C-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_005860.3(FSTL3):c.496C>T(p.Arg166Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000241 in 1,245,960 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R166S) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000018 ( 0 hom. )

Consequence

FSTL3
NM_005860.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.313

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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.496C>T	p.Arg166Cys	missense	Exon 3 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.496C>T	p.Arg166Cys	missense	Exon 3 of 5	ENSP00000166139.3	O95633-1
FSTL3	ENST00000905299.1		c.496C>T	p.Arg166Cys	missense	Exon 3 of 4	ENSP00000575358.1
FSTL3	ENST00000589185.2	TSL:2	c.163C>T	p.Arg55Cys	missense	Exon 1 of 2	ENSP00000484376.1	A0A087X1Q2

Frequencies

GnomAD3 genomes

AF:

0.00000659

AC:

AN:

151826

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000183

AC:

AN:

1094134

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

519818

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

22714

American (AMR)

AF:

0.00

AC:

AN:

8322

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14330

East Asian (EAS)

AF:

0.00

AC:

AN:

26250

South Asian (SAS)

AF:

0.00

AC:

AN:

26754

European-Finnish (FIN)

AF:

0.00

AC:

AN:

22126

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2930

European-Non Finnish (NFE)

AF:

0.00000216

AC:

AN:

926720

Other (OTH)

AF:

0.00

AC:

AN:

43988

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

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

AF:

0.00000659

AC:

AN:

151826

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74134

show subpopulations

African (AFR)

AF:

0.0000242

AC:

AN:

41350

American (AMR)

AF:

0.00

AC:

AN:

15258

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.00

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10552

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67906

Other (OTH)

AF:

0.00

AC:

AN:

2080

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.54

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.50

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.33

Eigen

Benign

-0.18

Eigen_PC

Benign

-0.31

FATHMM_MKL

Benign

0.17

LIST_S2

Benign

0.84

M_CAP

Pathogenic

0.54

MetaRNN

Uncertain

0.58

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.1

PhyloP100

0.31

PrimateAI

Uncertain

0.69

PROVEAN

Uncertain

-3.0

REVEL

Benign

0.13

Sift

Uncertain

0.010

Sift4G

Uncertain

0.027

Polyphen

1.0

Vest4

0.16

MutPred

0.64

Loss of MoRF binding (P = 0.0141)

MVP

0.59

MPC

1.6

ClinPred

0.98

GERP RS

0.58

PromoterAI

-0.062

Neutral

(source)

Varity_R

0.19

gMVP

0.65

Mutation Taster

=61/39

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

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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