14-24301636-A-T

Variant names:

• chr14-24301636-A-T
• NM_174913.3:c.722A>T

Variant summary

Our verdict is Uncertain significance. The variant received 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
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_174913.3. 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
	NOP9	NM_174913.3	MANE Select	c.722A>T	p.Glu241Val	missense	Exon 3 of 10	NP_777573.1	Q86U38-1
	NOP9	NM_001286367.2		c.722A>T	p.Glu241Val	missense	Exon 3 of 10	NP_001273296.1	Q86U38-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOP9	ENST00000267425.8	TSL:1 MANE Select	c.722A>T	p.Glu241Val	missense	Exon 3 of 10	ENSP00000267425.3	Q86U38-1
	NOP9	ENST00000396802.7	TSL:5	c.722A>T	p.Glu241Val	missense	Exon 3 of 10	ENSP00000380020.3	Q86U38-2
	NOP9	ENST00000650565.1		n.206A>T		non_coding_transcript_exon	Exon 2 of 11	ENSP00000497287.1	A0A3B3ISH6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		2.9
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.079
Sift	Uncertain	0.010	D
Sift4G	Uncertain	0.038	D
Polyphen		0.95	P
Vest4		0.40
MutPred		0.45		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
Mutation Taster		=84/16	polymorphism

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

Other links and lift over

hg19: chr14-24770842;