chr16-86579192-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_005250.3(FOXL1):​c.469C>T​(p.Pro157Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000219 in 1,595,196 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

FOXL1
NM_005250.3 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.678
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.018657535).
BS2
High AC in GnomAd4 at 9 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FOXL1NM_005250.3 linkc.469C>T p.Pro157Ser missense_variant Exon 1 of 1 ENST00000320241.5 NP_005241.1 Q12952Q498Y4

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FOXL1ENST00000320241.5 linkc.469C>T p.Pro157Ser missense_variant Exon 1 of 1 6 NM_005250.3 ENSP00000326272.3 Q12952
FOXL1ENST00000593625.1 linkc.*126C>T downstream_gene_variant 5 ENSP00000472376.1 M0R279

Frequencies

GnomAD3 genomes
AF:
0.0000592
AC:
9
AN:
152050
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000193
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000289
AC:
6
AN:
207646
Hom.:
0
AF XY:
0.0000175
AC XY:
2
AN XY:
114104
show subpopulations
Gnomad AFR exome
AF:
0.000535
Gnomad AMR exome
AF:
0.00
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:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000180
AC:
26
AN:
1443146
Hom.:
0
Cov.:
30
AF XY:
0.0000181
AC XY:
13
AN XY:
716546
show subpopulations
Gnomad4 AFR exome
AF:
0.000514
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:
0.00000453
Gnomad4 OTH exome
AF:
0.0000503
GnomAD4 genome
AF:
0.0000592
AC:
9
AN:
152050
Hom.:
0
Cov.:
33
AF XY:
0.0000539
AC XY:
4
AN XY:
74262
show subpopulations
Gnomad4 AFR
AF:
0.000193
Gnomad4 AMR
AF:
0.0000654
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000907
ExAC
AF:
0.0000262
AC:
3

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Dec 28, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.469C>T (p.P157S) 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 469, causing the proline (P) at amino acid position 157 to be replaced by a serine (S). 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
0.070
BayesDel_addAF
Benign
-0.35
T
BayesDel_noAF
Benign
-0.42
CADD
Benign
1.2
DANN
Benign
0.92
DEOGEN2
Benign
0.10
T
Eigen
Benign
-1.5
Eigen_PC
Benign
-1.5
FATHMM_MKL
Benign
0.058
N
LIST_S2
Benign
0.35
T
M_CAP
Benign
0.070
D
MetaRNN
Benign
0.019
T
MetaSVM
Uncertain
-0.24
T
MutationAssessor
Benign
0.0
N
PrimateAI
Uncertain
0.67
T
PROVEAN
Benign
-0.16
N
REVEL
Benign
0.24
Sift
Benign
0.72
T
Sift4G
Benign
0.51
T
Polyphen
0.0
B
Vest4
0.046
MutPred
0.27
Gain of phosphorylation at P157 (P = 0.0027);
MVP
0.61
ClinPred
0.019
T
GERP RS
-0.53
Varity_R
0.020
gMVP
0.25

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: rs778216107; hg19: chr16-86612798; API