20-2652732-AGGGCCTGGGCCT-AGGGCCTGGGCCTGGGCCTGGGCCTGGGCCTGGGCCTGGGCCTGGGCCTGGGCCTGGGCCTGGGCCTGGGCCTGGGCCTGGGCCT

Position:

• chr20-2652732-AGGGCCTGGGCCT-AGGGCCTGGGCCTGGGCCTGGGCCTGGGCCTGGGCCTGGGCCTGGGCCTGGGCCTGGGCCTGGGCCTGGGCCTGGGCCTGGGCCT

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_006392.4(NOP56):​c.4-85_4-84insGGCCTGGGCCTGGGCCTGGGCCTGGGCCTGGGCCTGGGCCTGGGCCTGGGCCTGGGCCTGGGCCTGGGCCTG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 0)
• Consequence: NOP56 NM_006392.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0470

Genes affected

NOP56 (HGNC:15911): (NOP56 ribonucleoprotein) Nop56p is a yeast nucleolar protein that is part of a complex with the nucleolar proteins Nop58p and fibrillarin. Nop56p is required for assembly of the 60S ribosomal subunit and is involved in pre-rRNA processing. The protein encoded by this gene is similar in sequence to Nop56p and is also found in the nucleolus. Expansion of a GGCCTG repeat from 3-8 copies to 1500-2500 copies in an intron of this gene results in spinocerebellar ataxia 36. Multiple transcript variants encoding several different isoforms have been found for this gene, but the full-length nature of most of them has not been determined. [provided by RefSeq, Jul 2016]

MIR1292 (HGNC:35364): (microRNA 1292) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NOP56	NM_006392.4	c.4-85_4-84insGGCCTGGGCCTGGGCCTGGGCCTGGGCCTGGGCCTGGGCCTGGGCCTGGGCCTGGGCCTGGGCCTGGGCCTG		intron_variant		ENST00000329276.10	NP_006383.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NOP56	ENST00000329276.10	c.4-85_4-84insGGCCTGGGCCTGGGCCTGGGCCTGGGCCTGGGCCTGGGCCTGGGCCTGGGCCTGGGCCTGGGCCTGGGCCTG		intron_variant		1	NM_006392.4	ENSP00000370589.3

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1555779353; hg19: chr20-2633378;