16-86578899-C-T
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_005250.3(FOXL1):c.176C>T(p.Ala59Val) variant causes a missense change. The variant allele was found at a frequency of 0.000209 in 1,614,174 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 0.00020 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00021 ( 0 hom. )
Consequence
FOXL1
NM_005250.3 missense
NM_005250.3 missense
Scores
4
6
4
Clinical Significance
Conservation
PhyloP100: 4.85
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 Likely_benign. Variant got -6 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.25477952).
BS2
?
High AC in GnomAd at 31 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FOXL1 | NM_005250.3 | c.176C>T | p.Ala59Val | missense_variant | 1/1 | ENST00000320241.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FOXL1 | ENST00000320241.5 | c.176C>T | p.Ala59Val | missense_variant | 1/1 | NM_005250.3 | P1 | ||
FOXL1 | ENST00000593625.1 | c.176C>T | p.Ala59Val | missense_variant | 2/2 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.000204 AC: 31AN: 152252Hom.: 0 Cov.: 33
GnomAD3 genomes
?
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GnomAD3 exomes AF: 0.000263 AC: 66AN: 251408Hom.: 0 AF XY: 0.000287 AC XY: 39AN XY: 135910
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GnomAD4 exome AF: 0.000210 AC: 307AN: 1461804Hom.: 0 Cov.: 30 AF XY: 0.000219 AC XY: 159AN XY: 727220
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GnomAD4 genome ? AF: 0.000203 AC: 31AN: 152370Hom.: 0 Cov.: 33 AF XY: 0.000242 AC XY: 18AN XY: 74514
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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 | Sep 17, 2021 | The c.176C>T (p.A59V) alteration is located in exon 1 (coding exon 1) of the FOXL1 gene. This alteration results from a C to T substitution at nucleotide position 176, causing the alanine (A) at amino acid position 59 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
Cadd
Pathogenic
Dann
Pathogenic
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D
M_CAP
Pathogenic
D
MetaRNN
Benign
T;T
MetaSVM
Pathogenic
D
MutationTaster
Benign
D
PrimateAI
Uncertain
T
Sift4G
Benign
T;D
Polyphen
0.23
.;B
Vest4
0.31
MVP
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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Score
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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