NM_000204.5:c.949C>T
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate
The NM_000204.5(CFI):c.949C>T(p.Arg317Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000698 in 1,590,590 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_000204.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CFI | ENST00000394634.7 | c.949C>T | p.Arg317Trp | missense_variant | Exon 9 of 13 | 1 | NM_000204.5 | ENSP00000378130.2 | ||
ENSG00000285330 | ENST00000645635.1 | c.949C>T | p.Arg317Trp | missense_variant | Exon 9 of 15 | ENSP00000493607.1 |
Frequencies
GnomAD3 genomes AF: 0.0000658 AC: 10AN: 151898Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000876 AC: 22AN: 251190Hom.: 0 AF XY: 0.0000810 AC XY: 11AN XY: 135788
GnomAD4 exome AF: 0.0000702 AC: 101AN: 1438574Hom.: 0 Cov.: 27 AF XY: 0.0000711 AC XY: 51AN XY: 717024
GnomAD4 genome AF: 0.0000658 AC: 10AN: 152016Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4AN XY: 74292
ClinVar
Submissions by phenotype
not provided Uncertain:2
This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 317 of the CFI protein (p.Arg317Trp). This variant is present in population databases (rs121964917, gnomAD 0.02%). This missense change has been observed in individual(s) with atypical hemolytic uremic syndrome (PMID: 16621965, 34169201). This variant is also known as R299W. ClinVar contains an entry for this variant (Variation ID: 12125). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt CFI protein function with a negative predictive value of 80%. Experimental studies are conflicting or provide insufficient evidence to determine the effect of this variant on CFI function (PMID: 17597211, 19877009). 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. -
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Atypical hemolytic-uremic syndrome with I factor anomaly;C3463916:Factor I deficiency;C3809523:Age related macular degeneration 13 Uncertain:1
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Atypical hemolytic-uremic syndrome with I factor anomaly Other:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at