3-138950555-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001040061.3(FOXL2NB):​c.511C>T​(p.Leu171Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,876 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

FOXL2NB
NM_001040061.3 missense

Scores

2
2
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.169
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 Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.054719597).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
FOXL2NBNM_001040061.3 linkuse as main transcriptc.511C>T p.Leu171Phe missense_variant 3/3 ENST00000383165.4 NP_001035150.1
FOXL2NBXM_005247443.4 linkuse as main transcriptc.442C>T p.Leu148Phe missense_variant 4/4 XP_005247500.1
FOXL2NBXM_024453517.2 linkuse as main transcriptc.*312C>T 3_prime_UTR_variant 2/2 XP_024309285.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
FOXL2NBENST00000383165.4 linkuse as main transcriptc.511C>T p.Leu171Phe missense_variant 3/32 NM_001040061.3 ENSP00000372651 P1
FOXL2NBENST00000498709.1 linkuse as main transcriptn.1440C>T non_coding_transcript_exon_variant 2/22
FOXL2NBENST00000470680.5 linkuse as main transcriptc.*393C>T 3_prime_UTR_variant, NMD_transcript_variant 3/33 ENSP00000418272

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.0000160
AC:
4
AN:
249542
Hom.:
0
AF XY:
0.0000295
AC XY:
4
AN XY:
135392
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000131
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000479
AC:
7
AN:
1461876
Hom.:
0
Cov.:
31
AF XY:
0.00000825
AC XY:
6
AN XY:
727236
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000696
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
32
ExAC
AF:
0.0000248
AC:
3

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 GeneticsApr 23, 2024The c.511C>T (p.L171F) alteration is located in exon 3 (coding exon 3) of the FOXL2NB gene. This alteration results from a C to T substitution at nucleotide position 511, causing the leucine (L) at amino acid position 171 to be replaced by a phenylalanine (F). 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
Uncertain
0.34
BayesDel_addAF
Benign
-0.42
T
BayesDel_noAF
Benign
-0.61
CADD
Benign
17
DANN
Uncertain
0.98
DEOGEN2
Benign
0.027
T
Eigen
Benign
-0.81
Eigen_PC
Benign
-0.90
FATHMM_MKL
Benign
0.16
N
LIST_S2
Benign
0.36
T
M_CAP
Benign
0.0054
T
MetaRNN
Benign
0.055
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.0
N
MutationTaster
Benign
1.0
N
PROVEAN
Benign
-2.0
N
REVEL
Benign
0.045
Sift
Pathogenic
0.0
D
Sift4G
Pathogenic
0.0
D
Polyphen
0.43
B
Vest4
0.074
MutPred
0.23
Gain of methylation at K170 (P = 0.025);
MVP
0.030
MPC
1.6
ClinPred
0.18
T
GERP RS
1.6
Varity_R
0.21
gMVP
0.019

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: rs754299081; hg19: chr3-138669397; API