X-47624325-G-A
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate
The NM_001145252.3(CFP):c.1360C>T(p.Pro454Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000031 in 1,098,033 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 18 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. P454A) 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 -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CFP | NM_001145252.3 | c.1360C>T | p.Pro454Ser | missense_variant | 9/9 | ENST00000396992.8 | |
CFP | NM_002621.2 | c.1360C>T | p.Pro454Ser | missense_variant | 10/10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CFP | ENST00000396992.8 | c.1360C>T | p.Pro454Ser | missense_variant | 9/9 | 1 | NM_001145252.3 | P1 | |
CFP | ENST00000247153.7 | c.1360C>T | p.Pro454Ser | missense_variant | 10/10 | 5 | P1 | ||
CFP | ENST00000478222.1 | n.481C>T | non_coding_transcript_exon_variant | 3/3 | 2 | ||||
CFP | ENST00000640573.1 | n.1598C>T | non_coding_transcript_exon_variant | 7/7 | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 22
GnomAD3 exomes AF: 0.00000545 AC: 1AN: 183522Hom.: 0 AF XY: 0.0000147 AC XY: 1AN XY: 67950
GnomAD4 exome AF: 0.0000310 AC: 34AN: 1098033Hom.: 0 Cov.: 30 AF XY: 0.0000495 AC XY: 18AN XY: 363387
GnomAD4 genome ? Cov.: 22
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 17, 2024 | The c.1360C>T (p.P454S) alteration is located in exon 10 (coding exon 9) of the CFP gene. This alteration results from a C to T substitution at nucleotide position 1360, causing the proline (P) at amino acid position 454 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 02, 2022 | 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 tolerated. This variant has not been reported in the literature in individuals affected with CFP-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 454 of the CFP protein (p.Pro454Ser). 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