16-86567443-C-G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_005251.3(FOXC2):​c.108C>G​(p.Ser36Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,460,990 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. S36S) has been classified as Benign.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

FOXC2
NM_005251.3 missense

Scores

2
9
8

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.521

Publications

0 publications found
Variant links:
Genes affected
FOXC2 (HGNC:3801): (forkhead box C2) 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 may play a role in the development of mesenchymal tissues. [provided by RefSeq, Jul 2008]
FOXC2-AS1 (HGNC:50665): (FOXC2 antisense RNA 1)

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.2160205).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FOXC2NM_005251.3 linkc.108C>G p.Ser36Arg missense_variant Exon 1 of 1 ENST00000649859.1 NP_005242.1 Q99958
FOXC2-AS1NR_125795.1 linkn.145+174G>C intron_variant Intron 1 of 1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FOXC2ENST00000649859.1 linkc.108C>G p.Ser36Arg missense_variant Exon 1 of 1 NM_005251.3 ENSP00000497759.1 Q99958

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1460990
Hom.:
0
Cov.:
32
AF XY:
0.00000138
AC XY:
1
AN XY:
726848
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33476
American (AMR)
AF:
0.00
AC:
0
AN:
44706
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26110
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39690
South Asian (SAS)
AF:
0.0000116
AC:
1
AN:
86238
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
52726
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1111902
Other (OTH)
AF:
0.00
AC:
0
AN:
60374
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.425
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.82
BayesDel_addAF
Uncertain
0.071
D
BayesDel_noAF
Benign
-0.14
CADD
Benign
22
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.49
T;T
Eigen
Benign
-0.36
Eigen_PC
Benign
-0.25
FATHMM_MKL
Uncertain
0.78
D
LIST_S2
Uncertain
0.89
.;D
M_CAP
Uncertain
0.12
D
MetaRNN
Benign
0.22
T;T
MetaSVM
Uncertain
-0.21
T
MutationAssessor
Benign
0.69
N;N
PhyloP100
0.52
PrimateAI
Pathogenic
0.81
D
PROVEAN
Benign
-2.1
.;N
REVEL
Benign
0.24
Sift
Uncertain
0.0080
.;D
Sift4G
Uncertain
0.050
.;T
Polyphen
0.45
P;P
Vest4
0.19
MutPred
0.30
Loss of glycosylation at S36 (P = 0.0057);Loss of glycosylation at S36 (P = 0.0057);
MVP
0.90
ClinPred
0.39
T
GERP RS
2.0
Varity_R
0.22
gMVP
0.65
Mutation Taster
=88/12
polymorphism

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

Other links and lift over

dbSNP: rs138318843; hg19: chr16-86601049; API