chr19-32881854-G-T
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_032816.5(CEP89):c.2125C>A(p.Gln709Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000499 in 1,601,984 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_032816.5 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 |
---|---|---|---|---|---|---|---|
CEP89 | NM_032816.5 | c.2125C>A | p.Gln709Lys | missense_variant | 18/19 | ENST00000305768.10 | |
CEP89 | XM_005259344.4 | c.2053C>A | p.Gln685Lys | missense_variant | 18/19 | ||
CEP89 | XM_047439562.1 | c.1384C>A | p.Gln462Lys | missense_variant | 12/13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CEP89 | ENST00000305768.10 | c.2125C>A | p.Gln709Lys | missense_variant | 18/19 | 1 | NM_032816.5 | P3 | |
CEP89 | ENST00000586984.6 | c.*734C>A | 3_prime_UTR_variant, NMD_transcript_variant | 17/18 | 1 | ||||
CEP89 | ENST00000591698.5 | c.*1459C>A | 3_prime_UTR_variant, NMD_transcript_variant | 17/18 | 2 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152230Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000422 AC: 1AN: 237040Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 128726
GnomAD4 exome AF: 0.00000414 AC: 6AN: 1449754Hom.: 0 Cov.: 31 AF XY: 0.00000277 AC XY: 2AN XY: 721082
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152230Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74366
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 25, 2023 | 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. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. This variant has not been reported in the literature in individuals affected with CEP89-related conditions. 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 sequence change replaces glutamine, which is neutral and polar, with lysine, which is basic and polar, at codon 709 of the CEP89 protein (p.Gln709Lys). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at