chrX-47624325-G-C
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4BS1_SupportingBS2
The NM_001145252.3(CFP):c.1360C>G(p.Pro454Ala) variant causes a missense change. The variant allele was found at a frequency of 0.0000331 in 1,207,908 control chromosomes in the GnomAD database, including 1 homozygotes. There are 10 hemizygotes in GnomAD. In-silico tool predicts a benign 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. P454S) has been classified as Uncertain significance.
Frequency
Consequence
NM_001145252.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CFP | NM_001145252.3 | c.1360C>G | p.Pro454Ala | missense_variant | 9/9 | ENST00000396992.8 | |
CFP | NM_002621.2 | c.1360C>G | p.Pro454Ala | missense_variant | 10/10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CFP | ENST00000396992.8 | c.1360C>G | p.Pro454Ala | missense_variant | 9/9 | 1 | NM_001145252.3 | P1 | |
CFP | ENST00000247153.7 | c.1360C>G | p.Pro454Ala | missense_variant | 10/10 | 5 | P1 | ||
CFP | ENST00000478222.1 | n.481C>G | non_coding_transcript_exon_variant | 3/3 | 2 | ||||
CFP | ENST00000640573.1 | n.1598C>G | non_coding_transcript_exon_variant | 7/7 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000364 AC: 4AN: 109821Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0AN XY: 32047
GnomAD3 exomes AF: 0.0000218 AC: 4AN: 183522Hom.: 0 AF XY: 0.0000294 AC XY: 2AN XY: 67950
GnomAD4 exome AF: 0.0000337 AC: 37AN: 1098033Hom.: 1 Cov.: 30 AF XY: 0.0000275 AC XY: 10AN XY: 363387
GnomAD4 genome ? AF: 0.0000273 AC: 3AN: 109875Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0AN XY: 32111
ClinVar
Submissions by phenotype
CFP-related disorder Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jul 10, 2023 | The CFP c.1360C>G variant is predicted to result in the amino acid substitution p.Pro454Ala. This variant occurs within the terminal exon, near the c-terminus. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0037% of alleles in individuals of European (Non-Finnish) descent in gnomAD, including two hemizygous individuals (http://gnomad.broadinstitute.org/variant/X-47483724-G-C). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jun 22, 2023 | This variant has not been reported in the literature in individuals affected with CFP-related conditions. This sequence change replaces proline, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 454 of the CFP protein (p.Pro454Ala). This variant is present in population databases (rs768994510, gnomAD 0.002%). ClinVar contains an entry for this variant (Variation ID: 1497624). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at