NM_174913.3:c.892C>T

Variant names:

• chr14-24302048-C-T
• rs1320853690
• NM_174913.3:c.892C>T

Variant summary

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

The NM_174913.3(NOP9):​c.892C>T​(p.His298Tyr) 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. 15/21 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: not found (cov: 33)
• Consequence: NOP9 NM_174913.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.371

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=0.13136038).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOP9	NM_174913.3	c.892C>T	p.His298Tyr	missense_variant	Exon 4 of 10	ENST00000267425.8	NP_777573.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOP9	ENST00000267425.8	c.892C>T	p.His298Tyr	missense_variant	Exon 4 of 10	1	NM_174913.3	ENSP00000267425.3
NOP9	ENST00000396802.7	c.892C>T	p.His298Tyr	missense_variant	Exon 4 of 10	5		ENSP00000380020.3
NOP9	ENST00000650565.1	n.376C>T		non_coding_transcript_exon_variant	Exon 3 of 11			ENSP00000497287.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 40

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	12
DANN	Benign	0.70
DEOGEN2	Benign	0.035	T;.
Eigen	Benign	-0.71
Eigen_PC	Benign	-0.61
FATHMM_MKL	Benign	0.72	D
M_CAP	Benign	0.0023	T
MetaRNN	Benign	0.13	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.3	L;L
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-1.6	N;N
REVEL	Benign	0.041
Sift	Benign	0.13	T;T
Sift4G	Benign	0.56	T;T
Polyphen		0.0	B;.
Vest4		0.27
MutPred		0.54		Gain of relative solvent accessibility (P = 0.1259);Gain of relative solvent accessibility (P = 0.1259);
MVP		0.31
MPC		0.27
ClinPred		0.045	T
GERP RS		2.4
Varity_R		0.042
gMVP		0.22

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs1320853690; hg19: chr14-24771254;