19-47745675-G-C

Variant names:

• chr19-47745675-G-C
• NM_015710.5:c.116G>C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_015710.5(NOP53):​c.116G>C​(p.Arg39Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: NOP53 NM_015710.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.56

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOP53	NM_015710.5	c.116G>C	p.Arg39Pro	missense_variant	Exon 1 of 13	ENST00000246802.10	NP_056525.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOP53	ENST00000246802.10	c.116G>C	p.Arg39Pro	missense_variant	Exon 1 of 13	1	NM_015710.5	ENSP00000246802.4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 07, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.116G>C (p.R39P) alteration is located in exon 1 (coding exon 1) of the GLTSCR2 gene. This alteration results from a G to C substitution at nucleotide position 116, causing the arginine (R) at amino acid position 39 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.49
BayesDel_addAF	Benign	-0.034	T
BayesDel_noAF	Benign	-0.29
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.26	T
Eigen	Benign	0.13
Eigen_PC	Benign	0.079
FATHMM_MKL	Benign	0.18	N
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.062	D
MetaRNN	Uncertain	0.53	D
MetaSVM	Benign	-0.96	T
PrimateAI	Uncertain	0.71	T
PROVEAN	Uncertain	-3.3	D
REVEL	Benign	0.14
Sift	Uncertain	0.014	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.50
MutPred		0.22		Gain of glycosylation at R39 (P = 0.009);
MVP		0.49
MPC		0.88
ClinPred		0.99	D
GERP RS		3.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.55
gMVP		0.12

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-48248932; COSMIC: COSV99622239; COSMIC: COSV99622239;