chr16-86579102-C-T
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_005250.3(FOXL1):c.379C>T(p.Pro127Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000122 in 1,613,870 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00016 ( 1 hom., cov: 33)
Exomes 𝑓: 0.00012 ( 0 hom. )
Consequence
FOXL1
NM_005250.3 missense
NM_005250.3 missense
Scores
5
9
5
Clinical Significance
Conservation
PhyloP100: 1.15
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 -4 ACMG points.
BS2
?
High AC in GnomAd at 25 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FOXL1 | NM_005250.3 | c.379C>T | p.Pro127Ser | missense_variant | 1/1 | ENST00000320241.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FOXL1 | ENST00000320241.5 | c.379C>T | p.Pro127Ser | missense_variant | 1/1 | NM_005250.3 | P1 | ||
FOXL1 | ENST00000593625.1 | downstream_gene_variant | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.000164 AC: 25AN: 152174Hom.: 1 Cov.: 33
GnomAD3 genomes
?
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GnomAD3 exomes AF: 0.000132 AC: 33AN: 250936Hom.: 0 AF XY: 0.000133 AC XY: 18AN XY: 135788
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GnomAD4 exome AF: 0.000118 AC: 172AN: 1461696Hom.: 0 Cov.: 30 AF XY: 0.000129 AC XY: 94AN XY: 727170
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GnomAD4 genome ? AF: 0.000164 AC: 25AN: 152174Hom.: 1 Cov.: 33 AF XY: 0.000215 AC XY: 16AN XY: 74348
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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 | Nov 15, 2021 | The c.379C>T (p.P127S) 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 379, causing the proline (P) at amino acid position 127 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
Uncertain
T
BayesDel_noAF
Pathogenic
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Pathogenic
D
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
D
LIST_S2
Uncertain
D
M_CAP
Uncertain
D
MetaRNN
Uncertain
D
MetaSVM
Pathogenic
D
MutationAssessor
Uncertain
M
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D
REVEL
Pathogenic
Sift
Uncertain
D
Sift4G
Uncertain
D
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