chr20-2652732-A-AGGGCCT

Variant names:

• chr20-2652732-A-AGGGCCT
• rs1555779353
• NM_006392.4:c.3+89_4-85dupGGCCTG

Variant summary

Our verdict is Likely benign. The variant received -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
• 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 671 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006392.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOP56	NM_006392.4	MANE Select	c.3+89_4-85dupGGCCTG		intron	N/A	NP_006383.2
	NOP56	NR_027700.3		n.32+89_33-85dupGGCCTG		intron	N/A
	NOP56	NR_145428.2		n.32+89_33-85dupGGCCTG		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOP56	ENST00000329276.10	TSL:1 MANE Select	c.3+89_4-85dupGGCCTG		intron	N/A	ENSP00000370589.3
	NOP56	ENST00000469588.5	TSL:2	n.107_112dupGGCCTG		non_coding_transcript_exon	Exon 1 of 5
	NOP56	ENST00000445139.1	TSL:5	c.3+89_4-85dupGGCCTG		intron	N/A	ENSP00000388497.1

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

African (AFR) AF: 0.0145 AC: 282 AN: 19488

American (AMR) AF: 0.00113 AC: 23 AN: 20360

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

East Asian (EAS) AF: 0.0000742 AC: 2 AN: 26970

South Asian (SAS) AF: 0.00305 AC: 174 AN: 57106

European-Finnish (FIN) AF: 0.0000829 AC: 3 AN: 36206

Middle Eastern (MID) AF: 0.000959 AC: 3 AN: 3128

European-Non Finnish (NFE) AF: 0.0000284 AC: 21 AN: 739266

Other (OTH) AF: 0.00151 AC: 63 AN: 41778

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

African (AFR) AF: 0.0153 AC: 615 AN: 40272

American (AMR) AF: 0.00133 AC: 19 AN: 14304

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 4802

South Asian (SAS) AF: 0.00475 AC: 22 AN: 4630

European-Finnish (FIN) AF: 0.000200 AC: 2 AN: 10010

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 280

European-Non Finnish (NFE) AF: 0.0000306 AC: 2 AN: 65420

Other (OTH) AF: 0.00538 AC: 11 AN: 2044

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.047
Mutation Taster		=100/0	polymorphism

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;