16-69748952-C-T

Variant names:

• chr16-69748952-C-T
• rs3811348
• NM_014062.3:c.692G>A

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 1P and 8B. PP3 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. 14/23 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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
• Publications: 36 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -7 ACMG points.

• PP3: Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.58 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014062.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOB1	NM_014062.3	MANE Select	c.692G>A	p.Arg231Gln	missense	Exon 6 of 9	NP_054781.1	Q9ULX3
	NOB1	NR_074074.2		n.577G>A		non_coding_transcript_exon	Exon 5 of 8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOB1	ENST00000268802.10	TSL:1 MANE Select	c.692G>A	p.Arg231Gln	missense	Exon 6 of 9	ENSP00000268802.5	Q9ULX3
	NOB1	ENST00000899343.1		c.692G>A	p.Arg231Gln	missense	Exon 6 of 9	ENSP00000569402.1
	NOB1	ENST00000920840.1		c.620G>A	p.Arg207Gln	missense	Exon 5 of 8	ENSP00000590899.1

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

GnomAD2 exomes AF: 0.494 AC: 122096 AN: 247368 AF XY: 0.504

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 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

African (AFR) AF: 0.159 AC: 5307 AN: 33446

American (AMR) AF: 0.440 AC: 19484 AN: 44296

Ashkenazi Jewish (ASJ) AF: 0.544 AC: 14176 AN: 26078

East Asian (EAS) AF: 0.241 AC: 9559 AN: 39650

South Asian (SAS) AF: 0.485 AC: 41703 AN: 86066

European-Finnish (FIN) AF: 0.602 AC: 32087 AN: 53324

Middle Eastern (MID) AF: 0.468 AC: 2652 AN: 5668

European-Non Finnish (NFE) AF: 0.587 AC: 651499 AN: 1110066

Other (OTH) AF: 0.517 AC: 31168 AN: 60274

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

African (AFR) AF: 0.169 AC: 7015 AN: 41542

American (AMR) AF: 0.463 AC: 7076 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.559 AC: 1942 AN: 3472

East Asian (EAS) AF: 0.197 AC: 1018 AN: 5166

South Asian (SAS) AF: 0.460 AC: 2214 AN: 4818

European-Finnish (FIN) AF: 0.584 AC: 6198 AN: 10604

Middle Eastern (MID) AF: 0.442 AC: 130 AN: 294

European-Non Finnish (NFE) AF: 0.585 AC: 39781 AN: 67992

Other (OTH) AF: 0.456 AC: 963 AN: 2110

Alfa AF: 0.509 Hom.: 25542

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 v4.9

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
PhyloP100		-0.41
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
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

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