16-69742600-T-A

Position:

chr16-69742600-T-A

Variant summary

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

The NM_014062.3(NOB1):c.971A>T(p.Tyr324Phe) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.000132 in 1,613,028 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00014 ( 1 hom. )

Consequence

NOB1
NM_014062.3 missense, splice_region

Scores

Splicing: ADA: 0.008658

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.54

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:

NQO1-DT (HGNC:55344): (NQO1 divergent transcript)

NQO1-DT links:

Genome browser will be placed here

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=0.2011647).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NOB1	NM_014062.3 linkuse as main transcript	c.971A>T	p.Tyr324Phe	missense_variant, splice_region_variant	9/9	ENST00000268802.10
NOB1	NR_074074.2 linkuse as main transcript	n.856A>T		splice_region_variant, non_coding_transcript_exon_variant	8/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
NOB1	ENST00000268802.10 linkuse as main transcript	c.971A>T	p.Tyr324Phe	missense_variant, splice_region_variant	9/9	1	NM_014062.3	P1
NOB1	ENST00000569871.5 linkuse as main transcript	c.*606A>T		splice_region_variant, 3_prime_UTR_variant, NMD_transcript_variant	8/8	5
NQO1-DT	ENST00000575838.1 linkuse as main transcript			downstream_gene_variant		5

Frequencies

GnomAD3 genomes

AF:

0.0000793

AC:

AN:

151360

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000243

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000289

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000382

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000884

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000148

AC:

AN:

250198

Hom.:

AF XY:

0.000147

AC XY:

AN XY:

135594

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000925

Gnomad NFE exome

AF:

0.000256

Gnomad OTH exome

AF:

0.000987

GnomAD4 exome

AF:

0.000138

AC:

201

AN:

1461668

Hom.:

Cov.:

AF XY:

0.000132

AC XY:

AN XY:

727092

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.0000765

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000318

Gnomad4 NFE exome

AF:

0.000149

Gnomad4 OTH exome

AF:

0.000248

GnomAD4 genome

AF:

0.0000793

AC:

AN:

151360

Hom.:

Cov.:

AF XY:

0.0000813

AC XY:

AN XY:

73810

show subpopulations

Gnomad4 AFR

AF:

0.0000243

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.000289

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000382

Gnomad4 NFE

AF:

0.0000884

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000145

Hom.:

Bravo

AF:

0.0000529

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00

AC:

ExAC

AF:

0.000255

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 11, 2022

The c.971A>T (p.Y324F) alteration is located in exon 9 (coding exon 9) of the NOB1 gene. This alteration results from a A to T substitution at nucleotide position 971, causing the tyrosine (Y) at amino acid position 324 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.32

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.060

Eigen

Benign

0.18

Eigen_PC

Uncertain

0.26

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.97

M_CAP

Benign

0.0073

MetaRNN

Benign

0.20

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.6

MutationTaster

Benign

1.0

PrimateAI

Benign

0.46

PROVEAN

Benign

-1.3

REVEL

Benign

0.15

Sift

Benign

0.59

Sift4G

Benign

0.82

Polyphen

0.43

Vest4

0.26

MVP

0.65

MPC

0.41

ClinPred

0.16

GERP RS

4.6

Varity_R

0.42

gMVP

0.45

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0087

dbscSNV1_RF

Benign

0.12

SpliceAI score (max)

0.10

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over