NM_001453.3:c.38T>C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_001453.3(FOXC1):ā€‹c.38T>Cā€‹(p.Leu13Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00000134 in 1,493,636 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: š‘“ 0.0000066 ( 0 hom., cov: 31)
Exomes š‘“: 7.4e-7 ( 0 hom. )

Consequence

FOXC1
NM_001453.3 missense

Scores

9
7
3

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.13
Variant links:
Genes affected
FOXC1 (HGNC:3800): (forkhead box C1) This gene belongs to the forkhead family of transcription factors which is characterized by a distinct DNA-binding forkhead domain. The specific function of this gene has not yet been determined; however, it has been shown to play a role in the regulation of embryonic and ocular development. Mutations in this gene cause various glaucoma phenotypes including primary congenital glaucoma, autosomal dominant iridogoniodysgenesis anomaly, and Axenfeld-Rieger anomaly. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.794

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FOXC1NM_001453.3 linkc.38T>C p.Leu13Pro missense_variant Exon 1 of 1 ENST00000645831.2 NP_001444.2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FOXC1ENST00000645831.2 linkc.38T>C p.Leu13Pro missense_variant Exon 1 of 1 NM_001453.3 ENSP00000493906.1 Q12948

Frequencies

GnomAD3 genomes
AF:
0.00000662
AC:
1
AN:
151086
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000196
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:
7.45e-7
AC:
1
AN:
1342550
Hom.:
0
Cov.:
31
AF XY:
0.00000152
AC XY:
1
AN XY:
658702
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:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.47e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000662
AC:
1
AN:
151086
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
73770
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000196
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.89
BayesDel_addAF
Pathogenic
0.19
D
BayesDel_noAF
Uncertain
0.040
CADD
Pathogenic
31
DANN
Uncertain
1.0
DEOGEN2
Pathogenic
0.80
D;D
Eigen
Uncertain
0.44
Eigen_PC
Uncertain
0.36
FATHMM_MKL
Benign
0.64
D
LIST_S2
Uncertain
0.89
.;D
M_CAP
Pathogenic
0.97
D
MetaRNN
Pathogenic
0.79
D;D
MetaSVM
Uncertain
0.78
D
MutationAssessor
Uncertain
2.1
M;M
PrimateAI
Pathogenic
0.97
D
PROVEAN
Pathogenic
-4.7
D;.
REVEL
Pathogenic
0.68
Sift
Pathogenic
0.0
D;.
Sift4G
Benign
0.081
T;.
Polyphen
1.0
D;D
Vest4
0.44
MutPred
0.39
Gain of disorder (P = 0.0043);Gain of disorder (P = 0.0043);
MVP
0.98
ClinPred
1.0
D
GERP RS
3.3
Varity_R
0.80
gMVP
0.75

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: rs1177304155; hg19: chr6-1610718; API