chr3-138947449-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001040061.3(FOXL2NB):ā€‹c.85T>Gā€‹(p.Ser29Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000725 in 1,516,466 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000059 ( 0 hom., cov: 32)
Exomes š‘“: 0.0000015 ( 0 hom. )

Consequence

FOXL2NB
NM_001040061.3 missense

Scores

2
1
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0240
Variant links:
Genes affected
FOXL2NB (HGNC:34428): (FOXL2 neighbor) Located in fibrillar center. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.16021779).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
FOXL2NBNM_001040061.3 linkuse as main transcriptc.85T>G p.Ser29Ala missense_variant 1/3 ENST00000383165.4 NP_001035150.1
FOXL2NBXM_005247443.4 linkuse as main transcriptc.-76T>G 5_prime_UTR_variant 1/4 XP_005247500.1
FOXL2NBXM_024453517.2 linkuse as main transcriptc.-175T>G 5_prime_UTR_variant 1/2 XP_024309285.1
FOXL2NBXM_024453518.2 linkuse as main transcriptc.-258T>G 5_prime_UTR_variant 1/3 XP_024309286.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
FOXL2NBENST00000383165.4 linkuse as main transcriptc.85T>G p.Ser29Ala missense_variant 1/32 NM_001040061.3 ENSP00000372651 P1
FOXL2NBENST00000470680.5 linkuse as main transcriptc.85T>G p.Ser29Ala missense_variant, NMD_transcript_variant 1/33 ENSP00000418272

Frequencies

GnomAD3 genomes
AF:
0.0000528
AC:
8
AN:
151404
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000194
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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
GnomAD4 exome
AF:
0.00000147
AC:
2
AN:
1364926
Hom.:
0
Cov.:
32
AF XY:
0.00000149
AC XY:
1
AN XY:
672410
show subpopulations
Gnomad4 AFR exome
AF:
0.0000657
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:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000594
AC:
9
AN:
151540
Hom.:
0
Cov.:
32
AF XY:
0.0000810
AC XY:
6
AN XY:
74098
show subpopulations
Gnomad4 AFR
AF:
0.000193
Gnomad4 AMR
AF:
0.00
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:
0.000474
Alfa
AF:
0.000132
Hom.:
0
Bravo
AF:
0.0000567

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsOct 26, 2021The c.85T>G (p.S29A) alteration is located in exon 1 (coding exon 1) of the FOXL2NB gene. This alteration results from a T to G substitution at nucleotide position 85, causing the serine (S) at amino acid position 29 to be replaced by an alanine (A). 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
0.16
BayesDel_addAF
Benign
-0.12
T
BayesDel_noAF
Benign
-0.42
CADD
Benign
19
DANN
Benign
0.88
DEOGEN2
Benign
0.021
T
Eigen
Benign
0.16
Eigen_PC
Benign
0.14
FATHMM_MKL
Uncertain
0.82
D
LIST_S2
Benign
0.24
T
M_CAP
Benign
0.039
D
MetaRNN
Benign
0.16
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.0
N
MutationTaster
Benign
1.0
N
PROVEAN
Benign
-1.5
N
REVEL
Benign
0.098
Sift
Pathogenic
0.0
D
Sift4G
Pathogenic
0.0
D
Polyphen
1.0
D
Vest4
0.15
MVP
0.27
MPC
0.88
ClinPred
0.42
T
GERP RS
2.5
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.0
Varity_R
0.39
gMVP
0.039

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: rs944287253; hg19: chr3-138666291; API