20-2652732-AGGGCCTGGGCCT-AGGGCCTGGGCCTGGGCCTGGGCCT

Variant names:

• chr20-2652732-A-AGGGCCTGGGCCT
• rs1555779353
• NM_006392.4:c.3+83_4-85dupGGCCTGGGCCTG

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_006392.4(NOP56):​c.3+83_4-85dupGGCCTGGGCCTG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000189 in 1,108,252 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000034 (0 hom., cov: 0)
  • Exomes 𝑓: 0.000017 (0 hom.)
• Consequence: NOP56 NM_006392.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0470
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BS2: High AC in GnomAd4 at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOP56	NM_006392.4	c.3+83_4-85dupGGCCTGGGCCTG		intron_variant	Intron 1 of 11	ENST00000329276.10	NP_006383.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOP56	ENST00000329276.10	c.3+83_4-85dupGGCCTGGGCCTG		intron_variant	Intron 1 of 11	1	NM_006392.4	ENSP00000370589.3

Frequencies

GnomAD3 genomes AF: 0.0000343 AC: 5 AN: 145898 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000996

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000153

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000166 AC: 16 AN: 962354 Hom.: 0 Cov.: 33 AF XY: 0.0000187 AC XY: 9 AN XY: 480058

African (AFR) AF: 0.00 AC: 0 AN: 19522

American (AMR) AF: 0.00 AC: 0 AN: 20360

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18014

East Asian (EAS) AF: 0.00 AC: 0 AN: 26970

South Asian (SAS) AF: 0.0000350 AC: 2 AN: 57116

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36206

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3128

European-Non Finnish (NFE) AF: 0.0000162 AC: 12 AN: 739260

Other (OTH) AF: 0.0000479 AC: 2 AN: 41778

GnomAD4 genome AF: 0.0000343 AC: 5 AN: 145898 Hom.: 0 Cov.: 0 AF XY: 0.0000422 AC XY: 3 AN XY: 71030

African (AFR) AF: 0.0000996 AC: 4 AN: 40162

American (AMR) AF: 0.00 AC: 0 AN: 14284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3368

East Asian (EAS) AF: 0.00 AC: 0 AN: 4818

South Asian (SAS) AF: 0.00 AC: 0 AN: 4636

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10010

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 304

European-Non Finnish (NFE) AF: 0.0000153 AC: 1 AN: 65426

Other (OTH) AF: 0.00 AC: 0 AN: 2020

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.047

Splicing

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

Other links and lift over

dbSNP: rs1555779353; hg19: chr20-2633378;