14-24408460-C-T
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Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP7
The NM_025081.3(NYNRIN):c.790C>T(p.Leu264=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000114 in 1,610,850 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000079 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00012 ( 0 hom. )
Consequence
NYNRIN
NM_025081.3 synonymous
NM_025081.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.194
Genes affected
NYNRIN (HGNC:20165): (NYN domain and retroviral integrase containing) Predicted to enable endoribonuclease activity and mRNA binding activity. Predicted to be involved in RNA phosphodiester bond hydrolysis, endonucleolytic. Predicted to be integral component of membrane. Predicted to be active in cytoplasmic ribonucleoprotein granule and nucleus. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.85).
BP7
Synonymous conserved (PhyloP=0.194 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NYNRIN | NM_025081.3 | c.790C>T | p.Leu264= | synonymous_variant | 3/9 | ENST00000382554.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NYNRIN | ENST00000382554.4 | c.790C>T | p.Leu264= | synonymous_variant | 3/9 | 5 | NM_025081.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000788 AC: 12AN: 152218Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000983 AC: 24AN: 244080Hom.: 0 AF XY: 0.0000977 AC XY: 13AN XY: 133056
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GnomAD4 exome AF: 0.000118 AC: 172AN: 1458632Hom.: 0 Cov.: 33 AF XY: 0.000116 AC XY: 84AN XY: 725318
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GnomAD4 genome AF: 0.0000788 AC: 12AN: 152218Hom.: 0 Cov.: 33 AF XY: 0.0000807 AC XY: 6AN XY: 74368
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 20, 2024 | This sequence change affects codon 264 of the NYNRIN mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the NYNRIN protein. This variant is present in population databases (rs756824618, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with NYNRIN-related conditions. Experimental studies and prediction algorithms are not available or were not evaluated, and the effect of this variant on mRNA splicing is currently unknown. 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
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at