14-24301636-A-T

Variant summary

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

The NM_174913.3(NOP9):c.722A>T(p.Glu241Val) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: NOP9 NM_174913.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.92

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NOP9	NM_174913.3	c.722A>T	p.Glu241Val	missense_variant	3/10	ENST00000267425.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NOP9	ENST00000267425.8	c.722A>T	p.Glu241Val	missense_variant	3/10	1	NM_174913.3	P1
NOP9	ENST00000396802.7	c.722A>T	p.Glu241Val	missense_variant	3/10	5
NOP9	ENST00000650565.1	c.206A>T	p.Glu69Val	missense_variant, NMD_transcript_variant	2/11

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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

Jul 29, 2022

The c.722A>T (p.E241V) alteration is located in exon 3 (coding exon 3) of the NOP9 gene. This alteration results from a A to T substitution at nucleotide position 722, causing the glutamic acid (E) at amino acid position 241 to be replaced by a valine (V). 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	0.091
BayesDel_addAF	Benign	-0.091	T
BayesDel_noAF	Benign	-0.37
Cadd	Pathogenic	29
Dann	Uncertain	0.99
DEOGEN2	Benign	0.038	T;.
Eigen	Uncertain	0.46
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Pathogenic	0.98	D
M_CAP	Benign	0.0088	T
MetaRNN	Benign	0.23	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.2	M;M
MutationTaster	Benign	0.97	D;D
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-2.0	N;N
REVEL	Benign	0.079
Sift	Uncertain	0.010	D;D
Sift4G	Uncertain	0.038	D;D
Polyphen		0.95	P;.
Vest4		0.40
MutPred		0.45		Loss of disorder (P = 0.039);Loss of disorder (P = 0.039);
MVP		0.43
MPC		0.29
ClinPred		0.84	D
GERP RS		5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.11
gMVP		0.30

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.46		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.46		Position offset: -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: chr14-24770842;