chr14-24302031-T-G

Variant names:

• chr14-24302031-T-G
• NM_174913.3:c.875T>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_174913.3(NOP9):​c.875T>G​(p.Leu292Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,686 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: NOP9 NM_174913.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.611
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08504948).

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.875T>G	p.Leu292Arg	missense	Exon 4 of 10	NP_777573.1	Q86U38-1
	NOP9	NM_001286367.2		c.875T>G	p.Leu292Arg	missense	Exon 4 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.875T>G	p.Leu292Arg	missense	Exon 4 of 10	ENSP00000267425.3	Q86U38-1
	NOP9	ENST00000396802.7	TSL:5	c.875T>G	p.Leu292Arg	missense	Exon 4 of 10	ENSP00000380020.3	Q86U38-2
	NOP9	ENST00000650565.1		n.359T>G		non_coding_transcript_exon	Exon 3 of 11	ENSP00000497287.1	A0A3B3ISH6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461686 Hom.: 0 Cov.: 39 AF XY: 0.00000138 AC XY: 1 AN XY: 727162

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53412

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5766

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111830

Other (OTH) AF: 0.00 AC: 0 AN: 60390

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	0.10
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	8.5
DANN	Benign	0.93
DEOGEN2	Benign	0.014	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.90
FATHMM_MKL	Benign	0.70	D
M_CAP	Benign	0.0058	T
MetaRNN	Benign	0.085	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L
PhyloP100		0.61
PrimateAI	Benign	0.40	T
PROVEAN	Benign	0.47	N
REVEL	Benign	0.019
Sift	Benign	0.42	T
Sift4G	Uncertain	0.0040	D
Polyphen		0.0050	B
Vest4		0.35
MutPred		0.55		Loss of helix (P = 0.0376)
MVP		0.17
MPC		0.35
ClinPred		0.080	T
GERP RS		1.3
PromoterAI		0.017	Neutral
Varity_R		0.040
gMVP		0.30
Mutation Taster		=85/15	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

hg19: chr14-24771237;