rs4280164

Variant names:

• chr14-24302079-G-A
• rs4280164
• NM_174913.3:c.923G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_174913.3(NOP9):​c.923G>A​(p.Ser308Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.196 in 1,613,460 control chromosomes in the GnomAD database, including 33,859 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.19 (3021 hom., cov: 33)
  • Exomes 𝑓: 0.20 (30838 hom.)
• Consequence: NOP9 NM_174913.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.17
• Publications: 54 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0020207465).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.28 is higher than 0.05.

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.923G>A	p.Ser308Asn	missense	Exon 4 of 10	NP_777573.1	Q86U38-1
	NOP9	NM_001286367.2		c.923G>A	p.Ser308Asn	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.923G>A	p.Ser308Asn	missense	Exon 4 of 10	ENSP00000267425.3	Q86U38-1
	NOP9	ENST00000396802.7	TSL:5	c.923G>A	p.Ser308Asn	missense	Exon 4 of 10	ENSP00000380020.3	Q86U38-2
	NOP9	ENST00000650565.1		n.407G>A		non_coding_transcript_exon	Exon 3 of 11	ENSP00000497287.1	A0A3B3ISH6

Frequencies

GnomAD3 genomes AF: 0.188 AC: 28521 AN: 152042 Hom.: 3020 Cov.: 33

Gnomad AFR AF: 0.171

Gnomad AMI AF: 0.127

Gnomad AMR AF: 0.287

Gnomad ASJ AF: 0.188

Gnomad EAS AF: 0.00192

Gnomad SAS AF: 0.106

Gnomad FIN AF: 0.132

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.205

Gnomad OTH AF: 0.189

GnomAD2 exomes AF: 0.191 AC: 47856 AN: 251178 AF XY: 0.181

Gnomad AFR exome AF: 0.172

Gnomad AMR exome AF: 0.385

Gnomad ASJ exome AF: 0.194

Gnomad EAS exome AF: 0.00158

Gnomad FIN exome AF: 0.137

Gnomad NFE exome AF: 0.196

Gnomad OTH exome AF: 0.198

GnomAD4 exome AF: 0.197 AC: 287201 AN: 1461300 Hom.: 30838 Cov.: 35 AF XY: 0.193 AC XY: 140155 AN XY: 726938

African (AFR) AF: 0.167 AC: 5600 AN: 33460

American (AMR) AF: 0.372 AC: 16635 AN: 44684

Ashkenazi Jewish (ASJ) AF: 0.196 AC: 5126 AN: 26112

East Asian (EAS) AF: 0.000781 AC: 31 AN: 39700

South Asian (SAS) AF: 0.113 AC: 9747 AN: 86194

European-Finnish (FIN) AF: 0.142 AC: 7579 AN: 53410

Middle Eastern (MID) AF: 0.115 AC: 663 AN: 5760

European-Non Finnish (NFE) AF: 0.208 AC: 230707 AN: 1111608

Other (OTH) AF: 0.184 AC: 11113 AN: 60372

GnomAD4 genome AF: 0.188 AC: 28534 AN: 152160 Hom.: 3021 Cov.: 33 AF XY: 0.182 AC XY: 13560 AN XY: 74382

African (AFR) AF: 0.171 AC: 7078 AN: 41488

American (AMR) AF: 0.287 AC: 4394 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.188 AC: 654 AN: 3470

East Asian (EAS) AF: 0.00193 AC: 10 AN: 5194

South Asian (SAS) AF: 0.106 AC: 510 AN: 4822

European-Finnish (FIN) AF: 0.132 AC: 1397 AN: 10574

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.205 AC: 13955 AN: 68000

Other (OTH) AF: 0.187 AC: 396 AN: 2114

Alfa AF: 0.197 Hom.: 15729

Bravo AF: 0.200

TwinsUK AF: 0.217 AC: 804

ALSPAC AF: 0.217 AC: 836

ESP6500AA AF: 0.167 AC: 736

ESP6500EA AF: 0.207 AC: 1783

ExAC AF: 0.183 AC: 22168

Asia WGS AF: 0.0630 AC: 218 AN: 3478

EpiCase AF: 0.192

EpiControl AF: 0.190

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.69	T
BayesDel_noAF	Benign	-0.62
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.029	T
Eigen	Uncertain	0.42
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Uncertain	0.91	D
MetaRNN	Benign	0.0020	T
MetaSVM	Benign	-0.87	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		3.2
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-0.32	N
REVEL	Benign	0.081
Sift	Benign	0.23	T
Sift4G	Uncertain	0.018	D
Polyphen		0.94	P
Vest4		0.14
MPC		0.44
ClinPred		0.030	T
GERP RS		5.2
PromoterAI		0.0032	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.071
gMVP		0.19
Mutation Taster		=97/3	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4280164; hg19: chr14-24771285; COSMIC: COSV51864854; COSMIC: COSV51864854;