Genetic Variant NOP56:c.3+71_4-85dupGGCCTGGGCCTGGGCCTGGGCCTG (chr20-2652732-A-AGGGCCTGGGCCTGGGCCTGGGCCT) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_006392.4(NOP56):c.3+71_4-85dupGGCCTGGGCCTGGGCCTGGGCCTG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000727 in 962,360 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. There is a variant allele frequency bias in the population database for this variant (GnomAdExome4), which may indicate mosaicism or somatic mutations in the reference population data. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 0)

Exomes 𝑓: 0.0000073 ( 0 hom. )

Consequence

NOP56
NM_006392.4 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0470

Publications

0 publications found

Variant links:

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]

NOP56 links:

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]

MIR1292 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOP56	NM_006392.4 link	c.3+71_4-85dupGGCCTGGGCCTGGGCCTGGGCCTG		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 link	c.3+71_4-85dupGGCCTGGGCCTGGGCCTGGGCCTG		intron_variant	Intron 1 of 11	1	NM_006392.4	ENSP00000370589.3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000727

AC:

AN:

962360

Hom.:

Cov.:

AF XY:

0.0000104

AC XY:

AN XY:

480058

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

19522

American (AMR)

AF:

0.0000491

AC:

AN:

20360

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18014

East Asian (EAS)

AF:

0.00

AC:

AN:

26970

South Asian (SAS)

AF:

0.000105

AC:

AN:

57116

European-Finnish (FIN)

AF:

0.00

AC:

AN:

36206

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3128

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

739266

Other (OTH)

AF:

0.00

AC:

AN:

41778

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000279027), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.382

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

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

Publications

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20-2652732-AGGGCCTGGGCCT-AGGGCCTGGGCCTGGGCCTGGGCCTGGGCCTGGGCCT

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over