chr16-86579393-G-A
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_005250.3(FOXL1):c.670G>A(p.Gly224Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00165 in 1,523,378 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0012 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0017 ( 4 hom. )
Consequence
FOXL1
NM_005250.3 missense
NM_005250.3 missense
Scores
1
2
16
Clinical Significance
Conservation
PhyloP100: 0.400
Genes affected
FOXL1 (HGNC:3817): (forkhead box L1) This gene encodes a member of the forkhead/winged helix-box (FOX) family of transcription factors. FOX transcription factors are characterized by a distinct DNA-binding forkhead domain and play critical roles in the regulation of multiple processes including metabolism, cell proliferation and gene expression during ontogenesis. [provided by RefSeq, Nov 2012]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -8 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.035634458).
BS2
?
High AC in GnomAd at 188 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FOXL1 | NM_005250.3 | c.670G>A | p.Gly224Ser | missense_variant | 1/1 | ENST00000320241.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FOXL1 | ENST00000320241.5 | c.670G>A | p.Gly224Ser | missense_variant | 1/1 | NM_005250.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00124 AC: 188AN: 152094Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.00104 AC: 124AN: 119230Hom.: 0 AF XY: 0.00103 AC XY: 67AN XY: 65278
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GnomAD4 exome AF: 0.00170 AC: 2332AN: 1371172Hom.: 4 Cov.: 35 AF XY: 0.00167 AC XY: 1129AN XY: 675776
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GnomAD4 genome ? AF: 0.00124 AC: 188AN: 152206Hom.: 0 Cov.: 33 AF XY: 0.00118 AC XY: 88AN XY: 74414
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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 | Dec 27, 2023 | The c.670G>A (p.G224S) alteration is located in exon 1 (coding exon 1) of the FOXL1 gene. This alteration results from a G to A substitution at nucleotide position 670, causing the glycine (G) at amino acid position 224 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T
M_CAP
Pathogenic
D
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
L
MutationTaster
Benign
N
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
T
Sift4G
Benign
T
Polyphen
B
Vest4
MVP
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at