chr3-138945678-G-C

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 1P and 2B. PP5BP4BS2_Supporting

The NM_023067.4(FOXL2):ā€‹c.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

Scores

4
8
7

Clinical Significance

Likely pathogenic no assertion criteria provided P:1O:1

Conservation

PhyloP100: 3.39
Variant links:
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]

Genome browser will be placed here

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
FOXL2NM_023067.4 linkuse as main transcriptc.1045C>G p.Arg349Gly missense_variant 1/1 ENST00000648323.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
FOXL2ENST00000648323.1 linkuse as main transcriptc.1045C>G p.Arg349Gly missense_variant 1/1 NM_023067.4 P1

Frequencies

GnomAD3 genomes
AF:
0.000211
AC:
32
AN:
151792
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000483
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00463
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.000192
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000442
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000338
AC:
79
AN:
233466
Hom.:
2
AF XY:
0.000358
AC XY:
46
AN XY:
128652
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.000418
Gnomad EAS exome
AF:
0.00284
Gnomad SAS exome
AF:
0.000372
Gnomad FIN exome
AF:
0.000375
Gnomad NFE exome
AF:
0.0000582
Gnomad OTH exome
AF:
0.000175
GnomAD4 exome
AF:
0.000166
AC:
237
AN:
1429562
Hom.:
3
Cov.:
31
AF XY:
0.000183
AC XY:
130
AN XY:
708580
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000227
Gnomad4 ASJ exome
AF:
0.000352
Gnomad4 EAS exome
AF:
0.00260
Gnomad4 SAS exome
AF:
0.000514
Gnomad4 FIN exome
AF:
0.000202
Gnomad4 NFE exome
AF:
0.0000522
Gnomad4 OTH exome
AF:
0.000256
GnomAD4 genome
AF:
0.000211
AC:
32
AN:
151908
Hom.:
0
Cov.:
33
AF XY:
0.000242
AC XY:
18
AN XY:
74264
show subpopulations
Gnomad4 AFR
AF:
0.0000482
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00465
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.000192
Gnomad4 NFE
AF:
0.0000442
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000112
Hom.:
0
Bravo
AF:
0.000268
ExAC
AF:
0.000266
AC:
32
Asia WGS
AF:
0.00173
AC:
6
AN:
3474

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 providedresearchCenter for Reproductive Medicine, Shandong Provincial Hospital Affiliated to Shandong UniversityOct 01, 2019- -
not specified Other:1
not provided, no classification providedreference populationITMISep 19, 2013- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.56
BayesDel_addAF
Benign
-0.075
T
BayesDel_noAF
Uncertain
0.11
CADD
Uncertain
24
DANN
Uncertain
0.99
DEOGEN2
Benign
0.37
T;T
Eigen
Uncertain
0.44
Eigen_PC
Uncertain
0.37
FATHMM_MKL
Uncertain
0.92
D
LIST_S2
Uncertain
0.86
.;D
M_CAP
Pathogenic
0.97
D
MetaRNN
Benign
0.029
T;T
MetaSVM
Uncertain
0.70
D
MutationAssessor
Benign
1.6
L;L
MutationTaster
Benign
1.0
D
PrimateAI
Pathogenic
0.94
D
PROVEAN
Benign
-1.6
.;N
REVEL
Pathogenic
0.76
Sift
Pathogenic
0.0
.;D
Sift4G
Benign
0.089
.;T
Polyphen
1.0
D;D
Vest4
0.45
MVP
0.74
ClinPred
0.073
T
GERP RS
3.4
Varity_R
0.27
gMVP
0.44

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: rs201840174; hg19: chr3-138664520; API