chr3-138945678-G-C
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Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 1P and 2B. PP5BP4BS2_Supporting
The NM_023067.4(FOXL2):āc.1045C>Gā(p.Arg349Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00017 in 1,581,470 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (no stars).
Frequency
Genomes: š 0.00021 ( 0 hom., cov: 33)
Exomes š: 0.00017 ( 3 hom. )
Consequence
FOXL2
NM_023067.4 missense
NM_023067.4 missense
Scores
4
8
7
Clinical Significance
Conservation
PhyloP100: 3.39
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 Likely_benign. Variant got -1 ACMG points.
PP5
Variant 3-138945678-G-C is Pathogenic according to our data. Variant chr3-138945678-G-C is described in ClinVar as [Likely_pathogenic]. Clinvar id is 134454.Status of the report is no_assertion_criteria_provided, 0 stars.
BP4
Computational evidence support a benign effect (MetaRNN=0.029051244). . Strength limited to SUPPORTING due to the PP5.
BS2
High AC in GnomAd4 at 32 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.1045C>G | p.Arg349Gly | missense_variant | 1/1 | ENST00000648323.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FOXL2 | ENST00000648323.1 | c.1045C>G | p.Arg349Gly | missense_variant | 1/1 | NM_023067.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000211 AC: 32AN: 151792Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000338 AC: 79AN: 233466Hom.: 2 AF XY: 0.000358 AC XY: 46AN XY: 128652
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GnomAD4 exome AF: 0.000166 AC: 237AN: 1429562Hom.: 3 Cov.: 31 AF XY: 0.000183 AC XY: 130AN XY: 708580
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GnomAD4 genome AF: 0.000211 AC: 32AN: 151908Hom.: 0 Cov.: 33 AF XY: 0.000242 AC XY: 18AN XY: 74264
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ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:1Other:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Genetic non-acquired premature ovarian failure Pathogenic:1
Likely pathogenic, no assertion criteria provided | research | Center for Reproductive Medicine, Shandong Provincial Hospital Affiliated to Shandong University | Oct 01, 2019 | - - |
not specified Other:1
not provided, no classification provided | reference population | ITMI | Sep 19, 2013 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
.;D
M_CAP
Pathogenic
D
MetaRNN
Benign
T;T
MetaSVM
Uncertain
D
MutationAssessor
Benign
L;L
MutationTaster
Benign
D
PrimateAI
Pathogenic
D
PROVEAN
Benign
.;N
REVEL
Pathogenic
Sift
Pathogenic
.;D
Sift4G
Benign
.;T
Polyphen
D;D
Vest4
0.45
MVP
0.74
ClinPred
T
GERP RS
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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