NM_002582.4:c.659+4_659+7delAGTA
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.
The NM_002582.4(PARN):c.659+4_659+7delAGTA variant causes a splice region, intron change. The variant allele was found at a frequency of 0.0000656 in 1,525,150 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_002582.4 splice_region, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000394 AC: 6AN: 152238Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000463 AC: 7AN: 151210Hom.: 0 AF XY: 0.0000623 AC XY: 5AN XY: 80218
GnomAD4 exome AF: 0.0000685 AC: 94AN: 1372912Hom.: 0 AF XY: 0.0000781 AC XY: 53AN XY: 678974
GnomAD4 genome AF: 0.0000394 AC: 6AN: 152238Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74384
ClinVar
Submissions by phenotype
Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 4;C4225356:Dyskeratosis congenita, autosomal recessive 6 Uncertain:2
This sequence change falls in intron 9 of the PARN gene. It does not directly change the encoded amino acid sequence of the PARN protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs759131762, gnomAD 0.01%). This variant has been observed in individual(s) with bone marrow failure (PMID: 25893599). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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. -
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Dyskeratosis congenita, autosomal recessive 6 Pathogenic:1
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not provided Uncertain:1
Intronic +5 splice site variant in a gene for which loss of function is a known mechanism of disease, and both splice predictors and evolutionary conservation support a deleterious effect, although in the absence of functional evidence the actual effect of this sequence change is unknown.; This variant is associated with the following publications: (PMID: 17576681, 9536098, 25893599) -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at