rs777090017
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 1P and 0B. PP3
The NM_002582.4(PARN):āc.1262A>Gā(p.Lys421Arg) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000118 in 1,436,458 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Consequence
NM_002582.4 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PARN | NM_002582.4 | c.1262A>G | p.Lys421Arg | missense_variant, splice_region_variant | 18/24 | ENST00000437198.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PARN | ENST00000437198.7 | c.1262A>G | p.Lys421Arg | missense_variant, splice_region_variant | 18/24 | 1 | NM_002582.4 | P1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.00000803 AC: 2AN: 248940Hom.: 0 AF XY: 0.00000740 AC XY: 1AN XY: 135062
GnomAD4 exome AF: 0.0000118 AC: 17AN: 1436458Hom.: 0 Cov.: 26 AF XY: 0.0000126 AC XY: 9AN XY: 716270
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 4 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | May 01, 2015 | - - |
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 | Invitae | Nov 12, 2022 | 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: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 190471). This missense change has been observed in individual(s) with pulmonary fibrosis (PMID: 25848748). This variant is present in population databases (rs777090017, gnomAD 0.002%). This sequence change replaces lysine, which is basic and polar, with arginine, which is basic and polar, at codon 421 of the PARN protein (p.Lys421Arg). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at