dbSNP rs753663363: FSTL3:p.Arg166Ser (chr19-680480-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_005860.3(FSTL3):c.496C>A(p.Arg166Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000104 in 1,246,066 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00057 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000040 ( 0 hom. )

Consequence

FSTL3
NM_005860.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

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: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.18512604).

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>A	p.Arg166Ser	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>A	p.Arg166Ser	missense	Exon 3 of 5	ENSP00000166139.3	O95633-1
FSTL3	ENST00000905299.1		c.496C>A	p.Arg166Ser	missense	Exon 3 of 4	ENSP00000575358.1
FSTL3	ENST00000589185.2	TSL:2	c.163C>A	p.Arg55Ser	missense	Exon 1 of 2	ENSP00000484376.1	A0A087X1Q2

Frequencies

GnomAD3 genomes

AF:

0.000566

AC:

AN:

151826

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00206

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:

0.000481

GnomAD2 exomes

AF:

0.00

AC:

AN:

620

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000402

AC:

AN:

1094134

Hom.:

Cov.:

AF XY:

0.0000442

AC XY:

AN XY:

519818

show subpopulations

African (AFR)

AF:

0.00158

AC:

AN:

22714

American (AMR)

AF:

0.000120

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:

26756

European-Finnish (FIN)

AF:

0.00

AC:

AN:

22126

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2930

European-Non Finnish (NFE)

AF:

0.00000108

AC:

AN:

926718

Other (OTH)

AF:

0.000136

AC:

AN:

43988

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

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:

0.000566

AC:

AN:

151932

Hom.:

Cov.:

AF XY:

0.000525

AC XY:

AN XY:

74250

show subpopulations

African (AFR)

AF:

0.00205

AC:

AN:

41466

American (AMR)

AF:

0.00

AC:

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5158

South Asian (SAS)

AF:

0.00

AC:

AN:

4814

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10552

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67896

Other (OTH)

AF:

0.000476

AC:

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.0000713

Hom.:

Bravo

AF:

0.000601

ExAC

AF:

0.0000607

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.65

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.12

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.91

FATHMM_MKL

Benign

0.077

LIST_S2

Benign

0.73

M_CAP

Pathogenic

0.48

MetaRNN

Benign

0.19

MetaSVM

Benign

-0.90

MutationAssessor

Benign

-0.13

PhyloP100

0.31

PrimateAI

Uncertain

0.65

PROVEAN

Benign

-0.87

REVEL

Benign

0.036

Sift

Benign

0.20

Sift4G

Benign

0.41

Polyphen

0.089

Vest4

0.14

MutPred

0.51

Loss of MoRF binding (P = 0.0408)

MVP

0.39

MPC

0.64

ClinPred

0.19

GERP RS

0.58

PromoterAI

-0.093

Neutral

(source)

Varity_R

0.19

gMVP

0.50

Mutation Taster

=62/38

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over