20-2652732-AGGGCCTGGGCCT-AGGGCCTGGGCCTGGGCCT

Position:

• chr20-2652732-AGGGCCTGGGCCT-AGGGCCTGGGCCTGGGCCT

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_006392.4(NOP56):​c.3+89_4-85dupGGCCTG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00112 in 1,108,316 control chromosomes in the GnomAD database, including 13 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0046 (5 hom., cov: 0)
  • Exomes 𝑓: 0.00059 (8 hom.)
• 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 Likely_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomAd4 at 671 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NOP56	NM_006392.4	c.3+89_4-85dupGGCCTG		intron_variant		ENST00000329276.10	NP_006383.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NOP56	ENST00000329276.10	c.3+89_4-85dupGGCCTG		intron_variant		1	NM_006392.4	ENSP00000370589.3

Frequencies

GnomAD3 genomes AF: 0.00452 AC: 660 AN: 145896 Hom.: 5 Cov.: 0

Gnomad AFR AF: 0.0151

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00133

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00475

Gnomad FIN AF: 0.000200

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000306

Gnomad OTH AF: 0.00495

GnomAD4 exome AF: 0.000593 AC: 571 AN: 962316 Hom.: 8 Cov.: 33 AF XY: 0.000596 AC XY: 286 AN XY: 480028

Gnomad4 AFR exome AF: 0.0145

Gnomad4 AMR exome AF: 0.00113

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000742

Gnomad4 SAS exome AF: 0.00305

Gnomad4 FIN exome AF: 0.0000829

Gnomad4 NFE exome AF: 0.0000284

Gnomad4 OTH exome AF: 0.00151

GnomAD4 genome AF: 0.00460 AC: 671 AN: 146000 Hom.: 5 Cov.: 0 AF XY: 0.00476 AC XY: 339 AN XY: 71144

Gnomad4 AFR AF: 0.0153

Gnomad4 AMR AF: 0.00133

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00475

Gnomad4 FIN AF: 0.000200

Gnomad4 NFE AF: 0.0000306

Gnomad4 OTH AF: 0.00538

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;