5-75677835-A-C
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001099271.2(POC5):āc.1523T>Gā(p.Ile508Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000663 in 1,612,812 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. I508M) has been classified as Uncertain significance.
Frequency
Consequence
NM_001099271.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
POC5 | NM_001099271.2 | c.1523T>G | p.Ile508Arg | missense_variant | 11/12 | ENST00000428202.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
POC5 | ENST00000428202.7 | c.1523T>G | p.Ile508Arg | missense_variant | 11/12 | 1 | NM_001099271.2 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000329 AC: 5AN: 152202Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000445 AC: 11AN: 247388Hom.: 0 AF XY: 0.0000521 AC XY: 7AN XY: 134330
GnomAD4 exome AF: 0.0000698 AC: 102AN: 1460610Hom.: 0 Cov.: 31 AF XY: 0.0000619 AC XY: 45AN XY: 726622
GnomAD4 genome AF: 0.0000329 AC: 5AN: 152202Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74348
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 28, 2022 | This variant is present in population databases (rs762351942, gnomAD 0.008%). This sequence change replaces isoleucine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 508 of the POC5 protein (p.Ile508Arg). This variant has not been reported in the literature in individuals affected with POC5-related conditions. 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Not Available"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Not Available"). ClinVar contains an entry for this variant (Variation ID: 1403089). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at