19-680304-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_005860.3(FSTL3):​c.320G>A​(p.Gly107Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000087 in 1,150,040 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 8.7e-7 ( 0 hom. )

Consequence

FSTL3
NM_005860.3 missense

Scores

4
11
4

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.33
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FSTL3NM_005860.3 linkc.320G>A p.Gly107Asp missense_variant Exon 3 of 5 ENST00000166139.9 NP_005851.1 O95633-1A0A024R1Y8

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FSTL3ENST00000166139.9 linkc.320G>A p.Gly107Asp missense_variant Exon 3 of 5 1 NM_005860.3 ENSP00000166139.3 O95633-1
FSTL3ENST00000589185 linkc.-14G>A 5_prime_UTR_variant Exon 1 of 2 2 ENSP00000484376.1 A0A087X1Q2
FSTL3ENST00000592058.3 linkn.54G>A non_coding_transcript_exon_variant Exon 2 of 4 5

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
8.70e-7
AC:
1
AN:
1150040
Hom.:
0
Cov.:
29
AF XY:
0.00000179
AC XY:
1
AN XY:
557754
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
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:
0.00000104
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.0000113

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Nov 30, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.320G>A (p.G107D) alteration is located in exon 3 (coding exon 3) of the FSTL3 gene. This alteration results from a G to A substitution at nucleotide position 320, causing the glycine (G) at amino acid position 107 to be replaced by an aspartic acid (D). 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
0.13
BayesDel_addAF
Pathogenic
0.20
D
BayesDel_noAF
Uncertain
0.060
CADD
Uncertain
24
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.45
T
Eigen
Uncertain
0.22
Eigen_PC
Uncertain
0.24
FATHMM_MKL
Uncertain
0.77
D
LIST_S2
Uncertain
0.87
D
M_CAP
Pathogenic
0.72
D
MetaRNN
Uncertain
0.62
D
MetaSVM
Uncertain
0.58
D
MutationAssessor
Uncertain
2.1
M
PrimateAI
Pathogenic
0.80
T
PROVEAN
Uncertain
-3.5
D
REVEL
Pathogenic
0.71
Sift
Benign
0.037
D
Sift4G
Benign
0.087
T
Polyphen
0.96
D
Vest4
0.22
MutPred
0.83
Gain of solvent accessibility (P = 0.0281);
MVP
0.95
MPC
0.81
ClinPred
0.97
D
GERP RS
3.6
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.73
gMVP
0.79

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.

Other links and lift over

dbSNP: rs1238641305; hg19: chr19-680304; API