rs4280164

chr14-24302079-G-A

Variant summary

Our verdict is Benign. Variant got -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. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• 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

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 Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NOP9	NM_174913.3	c.923G>A	p.Ser308Asn	missense_variant	4/10	ENST00000267425.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NOP9	ENST00000267425.8	c.923G>A	p.Ser308Asn	missense_variant	4/10	1	NM_174913.3	P1
NOP9	ENST00000396802.7	c.923G>A	p.Ser308Asn	missense_variant	4/10	5
NOP9	ENST00000650565.1	c.407G>A	p.Ser136Asn	missense_variant, NMD_transcript_variant	3/11

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

GnomAD3 exomes AF: 0.191 AC: 47856 AN: 251178 Hom.: 5831 AF XY: 0.181 AC XY: 24582 AN XY: 135742

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 SAS exome AF: 0.109

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

Gnomad4 AFR exome AF: 0.167

Gnomad4 AMR exome AF: 0.372

Gnomad4 ASJ exome AF: 0.196

Gnomad4 EAS exome AF: 0.000781

Gnomad4 SAS exome AF: 0.113

Gnomad4 FIN exome AF: 0.142

Gnomad4 NFE exome AF: 0.208

Gnomad4 OTH exome AF: 0.184

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

Gnomad4 AFR AF: 0.171

Gnomad4 AMR AF: 0.287

Gnomad4 ASJ AF: 0.188

Gnomad4 EAS AF: 0.00193

Gnomad4 SAS AF: 0.106

Gnomad4 FIN AF: 0.132

Gnomad4 NFE AF: 0.205

Gnomad4 OTH AF: 0.187

Alfa AF: 0.196 Hom.: 8059

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 v4.3

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;T
MetaSVM	Benign	-0.87	T
MutationAssessor	Uncertain	2.4	M;M
MutationTaster	Benign	0.13	P;P
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-0.32	N;N
REVEL	Benign	0.081
Sift	Benign	0.23	T;T
Sift4G	Uncertain	0.018	D;D
Polyphen		0.94	P;.
Vest4		0.14
MPC		0.44
ClinPred		0.030	T
GERP RS		5.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.071
gMVP		0.19

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