16-69748952-C-T

Position:

• chr16-69748952-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_014062.3(NOB1):​c.692G>A​(p.Arg231Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.543 in 1,611,064 control chromosomes in the GnomAD database, including 247,806 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/22 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.44 (17411 hom., cov: 33)
  • Exomes 𝑓: 0.55 (230395 hom.)
• Consequence: NOB1 NM_014062.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.410

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.58 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NOB1	NM_014062.3	c.692G>A	p.Arg231Gln	missense_variant	6/9	ENST00000268802.10	NP_054781.1
NOB1	NR_074074.2	n.577G>A		non_coding_transcript_exon_variant	5/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NOB1	ENST00000268802.10	c.692G>A	p.Arg231Gln	missense_variant	6/9	1	NM_014062.3	ENSP00000268802.5

Frequencies

GnomAD3 genomes AF: 0.440 AC: 66846 AN: 152078 Hom.: 17421 Cov.: 33

Gnomad AFR AF: 0.169

Gnomad AMI AF: 0.546

Gnomad AMR AF: 0.463

Gnomad ASJ AF: 0.559

Gnomad EAS AF: 0.197

Gnomad SAS AF: 0.460

Gnomad FIN AF: 0.584

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.585

Gnomad OTH AF: 0.459

GnomAD3 exomes AF: 0.494 AC: 122096 AN: 247368 Hom.: 32600 AF XY: 0.504 AC XY: 67405 AN XY: 133662

Gnomad AFR exome AF: 0.165

Gnomad AMR exome AF: 0.433

Gnomad ASJ exome AF: 0.548

Gnomad EAS exome AF: 0.182

Gnomad SAS exome AF: 0.483

Gnomad FIN exome AF: 0.597

Gnomad NFE exome AF: 0.587

Gnomad OTH exome AF: 0.521

GnomAD4 exome AF: 0.554 AC: 807635 AN: 1458868 Hom.: 230395 Cov.: 59 AF XY: 0.554 AC XY: 401850 AN XY: 725408

Gnomad4 AFR exome AF: 0.159

Gnomad4 AMR exome AF: 0.440

Gnomad4 ASJ exome AF: 0.544

Gnomad4 EAS exome AF: 0.241

Gnomad4 SAS exome AF: 0.485

Gnomad4 FIN exome AF: 0.602

Gnomad4 NFE exome AF: 0.587

Gnomad4 OTH exome AF: 0.517

GnomAD4 genome AF: 0.439 AC: 66832 AN: 152196 Hom.: 17411 Cov.: 33 AF XY: 0.436 AC XY: 32446 AN XY: 74408

Gnomad4 AFR AF: 0.169

Gnomad4 AMR AF: 0.463

Gnomad4 ASJ AF: 0.559

Gnomad4 EAS AF: 0.197

Gnomad4 SAS AF: 0.460

Gnomad4 FIN AF: 0.584

Gnomad4 NFE AF: 0.585

Gnomad4 OTH AF: 0.456

Alfa AF: 0.540 Hom.: 15099

Bravo AF: 0.416

TwinsUK AF: 0.591 AC: 2192

ALSPAC AF: 0.578 AC: 2227

ESP6500AA AF: 0.180 AC: 792

ESP6500EA AF: 0.570 AC: 4906

ExAC AF: 0.492 AC: 59762

Asia WGS AF: 0.371 AC: 1294 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.066
BayesDel_addAF	Benign	-0.79	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	14
DANN	Benign	0.93
DEOGEN2	Benign	0.0062	T
Eigen	Benign	-0.98
Eigen_PC	Benign	-0.84
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.84	T
MetaRNN	Benign	0.000027	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	-1.1	N
PrimateAI	Benign	0.23	T
PROVEAN	Benign	0.12	N
REVEL	Benign	0.071
Sift	Benign	0.64	T
Sift4G	Benign	0.56	T
Polyphen		0.0030	B
Vest4		0.030
MPC		0.15
ClinPred		0.0011	T
GERP RS		1.1
RBP_binding_hub_radar		1.0
RBP_regulation_power_radar		2.7
Varity_R		0.055
gMVP		0.18

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.78		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.78		Position offset: -1

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

Publications

LitVar

Other links and lift over

dbSNP: rs3811348; hg19: chr16-69782855; COSMIC: COSV52061557; COSMIC: COSV52061557;