chr5-75674556-G-T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001099271.2(POC5):c.1607C>A(p.Ala536Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000638 in 1,613,796 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. A536T) 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.1607C>A | p.Ala536Glu | missense_variant | 12/12 | ENST00000428202.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
POC5 | ENST00000428202.7 | c.1607C>A | p.Ala536Glu | missense_variant | 12/12 | 1 | NM_001099271.2 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000328 AC: 5AN: 152222Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000201 AC: 5AN: 249090Hom.: 0 AF XY: 0.0000222 AC XY: 3AN XY: 135122
GnomAD4 exome AF: 0.0000671 AC: 98AN: 1461574Hom.: 0 Cov.: 30 AF XY: 0.0000701 AC XY: 51AN XY: 727048
GnomAD4 genome ? AF: 0.0000328 AC: 5AN: 152222Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74368
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 13, 2023 | This sequence change replaces alanine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 536 of the POC5 protein (p.Ala536Glu). This variant is present in population databases (rs760243497, gnomAD 0.004%). This variant has not been reported in the literature in individuals affected with POC5-related conditions. ClinVar contains an entry for this variant (Variation ID: 1365847). 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. 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