16-14482695-C-G
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate
The ENST00000437198.7(PARN):āc.1613G>Cā(p.Arg538Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000576 in 1,613,674 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R538W) has been classified as Uncertain significance.
Frequency
Consequence
ENST00000437198.7 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 | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PARN | NM_002582.4 | c.1613G>C | p.Arg538Pro | missense_variant | 22/24 | ENST00000437198.7 | NP_002573.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PARN | ENST00000437198.7 | c.1613G>C | p.Arg538Pro | missense_variant | 22/24 | 1 | NM_002582.4 | ENSP00000387911 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000986 AC: 15AN: 152104Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000803 AC: 20AN: 249078Hom.: 0 AF XY: 0.000104 AC XY: 14AN XY: 135130
GnomAD4 exome AF: 0.0000534 AC: 78AN: 1461570Hom.: 0 Cov.: 31 AF XY: 0.0000674 AC XY: 49AN XY: 727076
GnomAD4 genome AF: 0.0000986 AC: 15AN: 152104Hom.: 0 Cov.: 32 AF XY: 0.0000673 AC XY: 5AN XY: 74294
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Aug 19, 2016 | - - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 18, 2020 | The c.1613G>C (p.R538P) alteration is located in exon 22 (coding exon 22) of the PARN gene. This alteration results from a G to C substitution at nucleotide position 1613, causing the arginine (R) at amino acid position 538 to be replaced by a proline (P). Based on data from the Genome Aggregation Database (gnomAD) database, the PARN c.1613G>C alteration was observed in 0.01% (21/280468) of total alleles studied, with a frequency of 0.02% (6/35286) in the Latino subpopulation. This amino acid position is well conserved in available vertebrate species. The p.R538P alteration is predicted to be tolerated by in silico analysis. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 4;C4225356:Dyskeratosis congenita, autosomal recessive 6 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 20, 2024 | This sequence change replaces arginine, which is basic and polar, with proline, which is neutral and non-polar, at codon 538 of the PARN protein (p.Arg538Pro). This variant is present in population databases (rs377199187, gnomAD 0.02%). This missense change has been observed in individual(s) with chronic hypersensitivity pneumonitis and telomeropathies (PMID: 30523342, 31268371). ClinVar contains an entry for this variant (Variation ID: 436156). 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