Variant chr3-120411962-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_007085.5(FSTL1):c.190C>G(p.Pro64Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00011 in 1,612,248 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00016 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00010 ( 0 hom. )

Consequence

FSTL1
NM_007085.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.87

Variant links:

Genes affected

FSTL1 (HGNC:3972): (follistatin like 1) This gene encodes a protein with similarity to follistatin, an activin-binding protein. It contains an FS module, a follistatin-like sequence containing 10 conserved cysteine residues. This gene product is thought to be an autoantigen associated with rheumatoid arthritis. [provided by RefSeq, Jul 2008]

FSTL1 links:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.34711564).

BS2

High AC in GnomAd4 at 25 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FSTL1	NM_007085.5 linkuse as main transcript	c.190C>G	p.Pro64Ala	missense_variant	4/11	ENST00000295633.8
LRRC58-DT	XR_007096031.1 linkuse as main transcript	n.964-3839G>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FSTL1	ENST00000295633.8 linkuse as main transcript	c.190C>G	p.Pro64Ala	missense_variant	4/11	1	NM_007085.5	P1	Q12841-1
	ENST00000494869.2 linkuse as main transcript	n.633-3839G>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.000165

AC:

AN:

151516

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000968

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:

0.000310

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000143

AC:

AN:

251272

Hom.:

AF XY:

0.0000957

AC XY:

AN XY:

135790

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.000405

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000123

Gnomad OTH exome

AF:

0.00114

GnomAD4 exome

AF:

0.000104

AC:

152

AN:

1460732

Hom.:

Cov.:

AF XY:

0.0000867

AC XY:

AN XY:

726626

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

Gnomad4 AMR exome

AF:

0.000425

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000110

Gnomad4 OTH exome

AF:

0.000133

GnomAD4 genome

AF:

0.000165

AC:

AN:

151516

Hom.:

Cov.:

AF XY:

0.0000540

AC XY:

AN XY:

74006

show subpopulations

Gnomad4 AFR

AF:

0.0000968

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000310

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000675

Hom.:

Bravo

AF:

0.000151

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000148

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 16, 2021

The c.190C>G (p.P64A) alteration is located in exon 4 (coding exon 3) of the FSTL1 gene. This alteration results from a C to G substitution at nucleotide position 190, causing the proline (P) at amino acid position 64 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.33

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.38

T;.;.

Eigen

Pathogenic

0.81

Eigen_PC

Pathogenic

0.77

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.93

D;D;D

M_CAP

Benign

0.014

MetaRNN

Benign

0.35

T;T;T

MetaSVM

Benign

-0.84

MutationAssessor

Uncertain

2.7

M;.;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Pathogenic

0.80

PROVEAN

Pathogenic

-6.2

D;D;D

REVEL

Uncertain

0.36

Sift

Benign

0.034

D;D;D

Sift4G

Benign

0.11

T;T;.

Polyphen

0.96

D;.;.

Vest4

0.51

MVP

0.38

MPC

0.52

ClinPred

0.16

GERP RS

5.3

Varity_R

0.42

gMVP

0.72

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over