rs140451304
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 6P and 2B. PM1PM2PM5BP4_Moderate
The NM_004928.3(CFAP410):c.218G>A(p.Arg73His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000248 in 1,612,638 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/18 in silico tools predict 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. R73P) has been classified as Likely pathogenic.
Frequency
Consequence
NM_004928.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CFAP410 | NM_004928.3 | c.218G>A | p.Arg73His | missense_variant | 4/7 | ENST00000339818.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CFAP410 | ENST00000339818.9 | c.218G>A | p.Arg73His | missense_variant | 4/7 | 1 | NM_004928.3 | P4 | |
ENST00000448927.1 | n.1705-14C>T | splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152248Hom.: 0 Cov.: 34
GnomAD3 exomes AF: 0.00000816 AC: 2AN: 245166Hom.: 0 AF XY: 0.00000750 AC XY: 1AN XY: 133252
GnomAD4 exome AF: 0.0000247 AC: 36AN: 1460390Hom.: 0 Cov.: 31 AF XY: 0.0000248 AC XY: 18AN XY: 726460
GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152248Hom.: 0 Cov.: 34 AF XY: 0.0000269 AC XY: 2AN XY: 74380
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 01, 2021 | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 73 of the CFAP410 protein (p.Arg73His). 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 CFAP410-related conditions. ClinVar contains an entry for this variant (Variation ID: 1053006). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The histidine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. This variant disrupts the p.Arg73 amino acid residue in CFAP410. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 26167768, 26974433, 27596865, 28041643). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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