14-24302350-C-A

Position:

• chr14-24302350-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_174913.3(NOP9):​c.1069C>A​(p.Gln357Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: NOP9 NM_174913.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.684

Genes affected

NOP9 (HGNC:19826): (NOP9 nucleolar protein) Enables RNA binding activity. Predicted to be involved in ribosome biogenesis. Predicted to be part of 90S preribosome and preribosome, small subunit precursor. Predicted to be active in nucleolus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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=0.18007499).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NOP9	NM_174913.3	c.1069C>A	p.Gln357Lys	missense_variant	5/10	ENST00000267425.8	NP_777573.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NOP9	ENST00000267425.8	c.1069C>A	p.Gln357Lys	missense_variant	5/10	1	NM_174913.3	ENSP00000267425	P1
NOP9	ENST00000396802.7	c.1069C>A	p.Gln357Lys	missense_variant	5/10	5		ENSP00000380020
NOP9	ENST00000650565.1	c.553C>A	p.Gln185Lys	missense_variant, NMD_transcript_variant	4/11			ENSP00000497287

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 26, 2021

The c.1069C>A (p.Q357K) alteration is located in exon 5 (coding exon 5) of the NOP9 gene. This alteration results from a C to A substitution at nucleotide position 1069, causing the glutamine (Q) at amino acid position 357 to be replaced by a lysine (K). 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	0.089
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	16
DANN	Benign	0.94
DEOGEN2	Benign	0.025	T;.
Eigen	Benign	-0.37
Eigen_PC	Benign	-0.22
FATHMM_MKL	Uncertain	0.78	D
M_CAP	Benign	0.0037	T
MetaRNN	Benign	0.18	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.3	M;M
MutationTaster	Benign	0.99	N;N
PrimateAI	Benign	0.44	T
PROVEAN	Benign	0.38	N;N
REVEL	Benign	0.051
Sift	Benign	0.30	T;T
Sift4G	Benign	0.61	T;T
Polyphen		0.058	B;.
Vest4		0.45
MutPred		0.39		Gain of ubiquitination at Q357 (P = 0.0351);Gain of ubiquitination at Q357 (P = 0.0351);
MVP		0.31
MPC		0.35
ClinPred		0.23	T
GERP RS		3.1
Varity_R		0.035
gMVP		0.29

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr14-24771556;