NM_174913.3:c.872A>C

Variant names:

• chr14-24302028-A-C
• NM_174913.3:c.872A>C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_174913.3(NOP9):​c.872A>C​(p.Lys291Thr) 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 1,461,852 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: NOP9 NM_174913.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.07

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.36571783).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOP9	NM_174913.3	c.872A>C	p.Lys291Thr	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.872A>C	p.Lys291Thr	missense_variant	Exon 4 of 10	1	NM_174913.3	ENSP00000267425.3
NOP9	ENST00000396802.7	c.872A>C	p.Lys291Thr	missense_variant	Exon 4 of 10	5		ENSP00000380020.3
NOP9	ENST00000650565.1	n.356A>C		non_coding_transcript_exon_variant	Exon 3 of 11			ENSP00000497287.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461852 Hom.: 0 Cov.: 39 AF XY: 0.00000138 AC XY: 1 AN XY: 727234

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	13
DANN	Uncertain	0.98
DEOGEN2	Benign	0.044	T;.
Eigen	Benign	-0.38
Eigen_PC	Benign	-0.47
FATHMM_MKL	Uncertain	0.91	D
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.37	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.6	M;M
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.92	N;N
REVEL	Benign	0.19
Sift	Benign	0.15	T;T
Sift4G	Pathogenic	0.0	D;D
Polyphen		0.96	D;.
Vest4		0.46
MutPred		0.65		Loss of ubiquitination at K291 (P = 0.0255);Loss of ubiquitination at K291 (P = 0.0255);
MVP		0.42
MPC		0.32
ClinPred		0.22	T
GERP RS		1.6
Varity_R		0.040
gMVP		0.40

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr14-24771234;