4-2462540-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001193282.4(CFAP99):c.1759G>A(p.Glu587Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000681 in 1,469,054 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 8/12 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. E587Q) has been classified as Uncertain significance.
Frequency
Consequence
NM_001193282.4 missense
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 |
---|---|---|---|---|---|---|---|
CFAP99 | NM_001193282.4 | c.1759G>A | p.Glu587Lys | missense_variant | 15/16 | ENST00000635017.2 | |
CFAP99 | XM_047415685.1 | c.1759G>A | p.Glu587Lys | missense_variant | 15/15 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CFAP99 | ENST00000635017.2 | c.1759G>A | p.Glu587Lys | missense_variant | 15/16 | 5 | NM_001193282.4 | P1 | |
RNF4 | ENST00000503659.5 | c.-223G>A | 5_prime_UTR_variant | 1/3 | 4 |
Frequencies
GnomAD3 genomes ? AF: 0.00000658 AC: 1AN: 152042Hom.: 0 Cov.: 32
GnomAD4 exome AF: 0.00000683 AC: 9AN: 1317012Hom.: 0 Cov.: 33 AF XY: 0.00000308 AC XY: 2AN XY: 648870
GnomAD4 genome ? AF: 0.00000658 AC: 1AN: 152042Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74262
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 08, 2022 | The c.1759G>A (p.E587K) alteration is located in exon 15 (coding exon 14) of the CFAP99 gene. This alteration results from a G to A substitution at nucleotide position 1759, causing the glutamic acid (E) at amino acid position 587 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at