Variant 3-138945678-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 1P and 5B. PP5BP4BS2

The NM_023067.4(FOXL2):c.1045C>G(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: 𝑓 0.00021 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00017 ( 3 hom. )

Consequence

FOXL2
NM_023067.4 missense

Scores

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]

FOXL2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 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 GnomAd at 32 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FOXL2	NM_023067.4 linkuse as main transcript	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 linkuse as main transcript	c.1045C>G	p.Arg349Gly	missense_variant	1/1		NM_023067.4	P1

Frequencies

GnomAD3 genomes

AF:

0.000211

AC:

AN:

151792

Hom.:

Cov.:

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:

AN:

233466

Hom.:

AF XY:

0.000358

AC XY:

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.:

Cov.:

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:

AN:

151908

Hom.:

Cov.:

AF XY:

0.000242

AC XY:

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.:

Bravo

AF:

0.000268

ExAC

AF:

0.000266

AC:

Asia WGS

AF:

0.00173

AC:

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 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: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.56

BayesDel_addAF

Benign

-0.075

BayesDel_noAF

Uncertain

0.11

Cadd

Uncertain

Dann

Uncertain

0.99

DEOGEN2

Benign

0.37

T;T

Eigen

Uncertain

0.44

Eigen_PC

Uncertain

0.37

FATHMM_MKL

Uncertain

0.92

M_CAP

Pathogenic

0.97

MetaRNN

Benign

0.029

T;T

MetaSVM

Uncertain

0.70

MutationAssessor

Benign

1.6

L;L

MutationTaster

Benign

1.0

PrimateAI

Pathogenic

0.94

Polyphen

1.0

D;D

Vest4

0.45

MVP

0.74

ClinPred

0.073

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over