chr19-860619-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001928.4(CFD):c.58G>A(p.Ala20Thr) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000345 in 1,448,174 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. 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. A20V) has been classified as Uncertain significance.
Frequency
Consequence
NM_001928.4 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CFD | NM_001928.4 | c.58G>A | p.Ala20Thr | missense_variant, splice_region_variant | 2/5 | ENST00000327726.11 | |
CFD | NM_001317335.2 | c.79G>A | p.Ala27Thr | missense_variant, splice_region_variant | 2/5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CFD | ENST00000327726.11 | c.58G>A | p.Ala20Thr | missense_variant, splice_region_variant | 2/5 | 1 | NM_001928.4 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.00000658 AC: 1AN: 151946Hom.: 0 Cov.: 30
GnomAD3 exomes AF: 0.0000665 AC: 4AN: 60138Hom.: 0 AF XY: 0.0000858 AC XY: 3AN XY: 34960
GnomAD4 exome AF: 0.00000309 AC: 4AN: 1296228Hom.: 0 Cov.: 30 AF XY: 0.00000314 AC XY: 2AN XY: 636712
GnomAD4 genome ? AF: 0.00000658 AC: 1AN: 151946Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 74218
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | May 29, 2022 | This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 20 of the CFD protein (p.Ala20Thr). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with CFD-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Not Available"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Not Available"). 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