19-47745592-G-C

Variant names:

• chr19-47745592-G-C
• rs376292602
• NM_015710.5:c.33G>C

Variant summary

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

The NM_015710.5(NOP53):​c.33G>C​(p.Lys11Asn) 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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: NOP53 NM_015710.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.927
• Publications: 0 publications found

Genes affected

NOP53 (HGNC:4333): (NOP53 ribosome biogenesis factor) Enables 5S rRNA binding activity; identical protein binding activity; and p53 binding activity. Involved in several processes, including negative regulation of transcription, DNA-templated; regulation of cellular protein metabolic process; and regulation of intracellular signal transduction. Located in cytosol; fibrillar center; and nucleoplasm. Colocalizes with rDNA heterochromatin. [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=0.081632614).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015710.5. 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
	NOP53	NM_015710.5	MANE Select	c.33G>C	p.Lys11Asn	missense	Exon 1 of 13	NP_056525.2	Q9NZM5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOP53	ENST00000246802.10	TSL:1 MANE Select	c.33G>C	p.Lys11Asn	missense	Exon 1 of 13	ENSP00000246802.4	Q9NZM5
	NOP53	ENST00000594525.5	TSL:1	n.42G>C		non_coding_transcript_exon	Exon 1 of 6
	NOP53	ENST00000856732.1		c.33G>C	p.Lys11Asn	missense	Exon 1 of 13	ENSP00000526791.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251184 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	7.4
DANN	Benign	0.94
DEOGEN2	Benign	0.032	T
Eigen	Benign	-0.92
Eigen_PC	Benign	-0.96
FATHMM_MKL	Benign	0.015	N
LIST_S2	Benign	0.43	T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.082	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.93
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.70	N
REVEL	Benign	0.066
Sift	Benign	0.045	D
Sift4G	Benign	0.087	T
Polyphen		0.020	B
Vest4		0.26
MutPred		0.16		Loss of ubiquitination at K11 (P = 0.0043)
MVP		0.25
MPC		0.23
ClinPred		0.15	T
GERP RS		0.63
PromoterAI		0.0013	Neutral
Varity_R		0.095
gMVP		0.091
Mutation Taster		=95/5	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs376292602; hg19: chr19-48248849;