20-2652820-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_006392.4(NOP56):c.4-22C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00191 in 1,604,186 control chromosomes in the GnomAD database, including 62 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.011 ( 25 hom., cov: 33)

Exomes 𝑓: 0.0010 ( 37 hom. )

Consequence

NOP56
NM_006392.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.25

Publications

4 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: Benign. The variant received -12 ACMG points.

BP4

This position, referring to a specific DNA site, is a probable branch point but is likely benign (scored 2 / 10, using the threshold of <=3). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0105 (1600/152016) while in subpopulation AFR AF = 0.0363 (1507/41522). AF 95% confidence interval is 0.0348. There are 25 homozygotes in GnomAd4. There are 775 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High AC in GnomAd4 at 1600 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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
NOP56	NM_006392.4	MANE Select	c.4-22C>T	intron	N/A	NP_006383.2
MIR1292	NR_031699.1		n.44C>T	non_coding_transcript_exon	Exon 1 of 1
NOP56	NR_027700.3		n.33-22C>T	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NOP56	ENST00000329276.10	TSL:1 MANE Select	c.4-22C>T	intron	N/A	ENSP00000370589.3	O00567
NOP56	ENST00000860469.1		c.4-22C>T	intron	N/A	ENSP00000530528.1
NOP56	ENST00000945682.1		c.4-22C>T	intron	N/A	ENSP00000615741.1

Frequencies

GnomAD3 genomes

AF:

0.0105

AC:

1596

AN:

151894

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0363

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00513

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000442

Gnomad OTH

AF:

0.00525

GnomAD2 exomes

AF:

0.00250

AC:

568

AN:

227416

AF XY:

0.00190

show subpopulations

Gnomad AFR exome

AF:

0.0350

Gnomad AMR exome

AF:

0.00198

Gnomad ASJ exome

AF:

0.000106

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000504

Gnomad OTH exome

AF:

0.00196

GnomAD4 exome

AF:

0.00100

AC:

1459

AN:

1452170

Hom.:

Cov.:

AF XY:

0.000809

AC XY:

584

AN XY:

721920

show subpopulations

African (AFR)

AF:

0.0364

AC:

1202

AN:

33048

American (AMR)

AF:

0.00221

AC:

AN:

43936

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25898

East Asian (EAS)

AF:

0.00

AC:

AN:

39206

South Asian (SAS)

AF:

0.000118

AC:

AN:

85050

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51254

Middle Eastern (MID)

AF:

0.000915

AC:

AN:

5464

European-Non Finnish (NFE)

AF:

0.0000162

AC:

AN:

1108352

Other (OTH)

AF:

0.00212

AC:

127

AN:

59962

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.516

Heterozygous variant carriers

152

227

303

379

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

126

168

210

<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

AF:

0.0105

AC:

1600

AN:

152016

Hom.:

Cov.:

AF XY:

0.0104

AC XY:

775

AN XY:

74322

show subpopulations

African (AFR)

AF:

0.0363

AC:

1507

AN:

41522

American (AMR)

AF:

0.00513

AC:

AN:

15214

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3464

East Asian (EAS)

AF:

0.00

AC:

AN:

5144

South Asian (SAS)

AF:

0.000207

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0000442

AC:

AN:

67922

Other (OTH)

AF:

0.00520

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

180

270

360

450

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00367

Hom.:

Bravo

AF:

0.0121

Asia WGS

AF:

0.00346

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

1.0

(source)

DANN

Benign

0.93

PhyloP100

-3.3

BranchPoint Hunter

2.0

PromoterAI

0.019

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over