4-2462540-G-C
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_001193282.4(CFAP99):āc.1759G>Cā(p.Glu587Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000211 in 1,469,162 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 9/12 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E587K) has been classified as Uncertain significance.
Frequency
Consequence
NM_001193282.4 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 |
---|---|---|---|---|---|---|---|
CFAP99 | NM_001193282.4 | c.1759G>C | p.Glu587Gln | missense_variant | 15/16 | ENST00000635017.2 | |
CFAP99 | XM_047415685.1 | c.1759G>C | p.Glu587Gln | missense_variant | 15/15 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CFAP99 | ENST00000635017.2 | c.1759G>C | p.Glu587Gln | missense_variant | 15/16 | 5 | NM_001193282.4 | P1 | |
RNF4 | ENST00000503659.5 | c.-223G>C | 5_prime_UTR_variant | 1/3 | 4 |
Frequencies
GnomAD3 genomes AF: 0.0000658 AC: 10AN: 152042Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000406 AC: 3AN: 73888Hom.: 0 AF XY: 0.0000467 AC XY: 2AN XY: 42810
GnomAD4 exome AF: 0.0000159 AC: 21AN: 1317012Hom.: 0 Cov.: 33 AF XY: 0.0000170 AC XY: 11AN XY: 648870
GnomAD4 genome AF: 0.0000657 AC: 10AN: 152150Hom.: 0 Cov.: 32 AF XY: 0.0000807 AC XY: 6AN XY: 74380
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 22, 2023 | The c.1759G>C (p.E587Q) alteration is located in exon 15 (coding exon 14) of the CFAP99 gene. This alteration results from a G to C substitution at nucleotide position 1759, causing the glutamic acid (E) at amino acid position 587 to be replaced by a glutamine (Q). 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