rs28937885
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PP3_ModerateBS2_Supporting
The NM_023067.4(FOXL2):c.772T>A(p.Tyr258Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000709 in 1,409,958 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000071 ( 0 hom. )
Consequence
FOXL2
NM_023067.4 missense
NM_023067.4 missense
Scores
6
6
7
Clinical Significance
Conservation
PhyloP100: 1.83
Genes affected
FOXL2 (HGNC:1092): (forkhead box L2) This gene encodes a forkhead transcription factor. The protein contains a fork-head DNA-binding domain and may play a role in ovarian development and function. Expansion of a polyalanine repeat region and other mutations in this gene are a cause of blepharophimosis syndrome and premature ovarian failure 3. [provided by RefSeq, Jul 2016]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PP3
MetaRNN computational evidence supports a deleterious effect, 0.867
BS2
High AC in GnomAdExome4 at 9 AD gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FOXL2 | NM_023067.4 | c.772T>A | p.Tyr258Asn | missense_variant | 1/1 | ENST00000648323.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FOXL2 | ENST00000648323.1 | c.772T>A | p.Tyr258Asn | missense_variant | 1/1 | NM_023067.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00000663 AC: 1AN: 150844Hom.: 0 Cov.: 32
GnomAD3 genomes
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GnomAD4 exome AF: 0.00000715 AC: 9AN: 1259114Hom.: 0 Cov.: 32 AF XY: 0.0000129 AC XY: 8AN XY: 617976
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GnomAD4 genome AF: 0.00000663 AC: 1AN: 150844Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 73678
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ClinVar
Significance: Uncertain significance
Submissions summary: Pathogenic:1Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Premature ovarian failure 3 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Aug 01, 2002 | - - |
Blepharophimosis, ptosis, and epicanthus inversus syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Mendelics | May 28, 2019 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Benign
DEOGEN2
Benign
T;T
Eigen
Uncertain
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
.;D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D
MetaSVM
Uncertain
D
MutationAssessor
Benign
L;L
MutationTaster
Benign
A
PrimateAI
Pathogenic
D
PROVEAN
Benign
.;N
REVEL
Uncertain
Sift
Pathogenic
.;D
Sift4G
Benign
.;T
Polyphen
D;D
Vest4
0.75
MutPred
Loss of phosphorylation at Y258 (P = 0.0085);Loss of phosphorylation at Y258 (P = 0.0085);
MVP
0.93
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