Variant 16-69748952-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_014062.3(NOB1):c.692G>T(p.Arg231Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,110 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R231Q) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Consequence

NOB1
NM_014062.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.410

Variant links:

Genes affected

NOB1 (HGNC:29540): (NIN1 (RPN12) binding protein 1 homolog) In yeast, over 200 protein and RNA cofactors are required for ribosome assembly, and these are generally conserved in eukaryotes. These factors orchestrate modification and cleavage of the initial 35S precursor rRNA transcript into the mature 18S, 5.8S, and 25S rRNAs, folding of the rRNA, and binding of ribosomal proteins and 5S RNA. Nob1 is involved in pre-rRNA processing. In a late cytoplasmic processing step, Nob1 cleaves a 20S rRNA intermediate at cleavage site D to produce the mature 18S rRNA (Lamanna and Karbstein, 2009 [PubMed 19706509]).[supplied by OMIM, Nov 2010]

NOB1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.12143132).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NOB1	NM_014062.3 linkuse as main transcript	c.692G>T	p.Arg231Leu	missense_variant	6/9	ENST00000268802.10	NP_054781.1
NOB1	NR_074074.2 linkuse as main transcript	n.577G>T		non_coding_transcript_exon_variant	5/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
NOB1	ENST00000268802.10 linkuse as main transcript	c.692G>T	p.Arg231Leu	missense_variant	6/9	1	NM_014062.3	ENSP00000268802	P1
NOB1	ENST00000561677.6 linkuse as main transcript	n.378G>T		non_coding_transcript_exon_variant	4/4	2
NOB1	ENST00000564620.5 linkuse as main transcript	c.*360G>T		3_prime_UTR_variant, NMD_transcript_variant	5/7	2		ENSP00000456710
NOB1	ENST00000569871.5 linkuse as main transcript	c.*360G>T		splice_region_variant, 3_prime_UTR_variant, NMD_transcript_variant	5/8	5		ENSP00000457760

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152110

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152110

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74302

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.097

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.022

Eigen

Benign

-0.82

Eigen_PC

Benign

-0.74

FATHMM_MKL

Benign

0.24

LIST_S2

Uncertain

0.94

M_CAP

Benign

0.019

MetaRNN

Benign

0.12

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.55

MutationTaster

Benign

1.0

PrimateAI

Benign

0.25

PROVEAN

Benign

-1.7

REVEL

Benign

0.062

Sift

Benign

0.30

Sift4G

Benign

0.27

Polyphen

0.020

Vest4

0.41

MutPred

0.40

Loss of sheet (P = 0.0817);

MVP

0.28

MPC

0.18

ClinPred

0.093

GERP RS

1.1

RBP_binding_hub_radar

1.0

RBP_regulation_power_radar

2.7

Varity_R

0.095

gMVP

0.37

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over