16-86567496-G-T
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP3BS2
The NM_005251.3(FOXC2):c.161G>T(p.Arg54Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000434 in 1,613,742 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R54H) has been classified as Uncertain significance.
Frequency
Consequence
NM_005251.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FOXC2 | NM_005251.3 | c.161G>T | p.Arg54Leu | missense_variant | 1/1 | ENST00000649859.1 | |
FOXC2-AS1 | NR_125795.1 | n.145+121C>A | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FOXC2 | ENST00000649859.1 | c.161G>T | p.Arg54Leu | missense_variant | 1/1 | NM_005251.3 | P1 | ||
FOXC2-AS1 | ENST00000563280.3 | n.231+121C>A | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152164Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000797 AC: 2AN: 250968Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135788
GnomAD4 exome AF: 0.00000411 AC: 6AN: 1461578Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1AN XY: 727102
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152164Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74342
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 20, 2022 | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. This variant has not been reported in the literature in individuals affected with FOXC2-related conditions. This variant is present in population databases (rs746195395, gnomAD 0.002%). This sequence change replaces arginine, which is basic and polar, with leucine, which is neutral and non-polar, at codon 54 of the FOXC2 protein (p.Arg54Leu). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at