19-47745677-G-A

Variant names:

• chr19-47745677-G-A
• NM_015710.5:c.118G>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015710.5(NOP53):​c.118G>A​(p.Gly40Ser) 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. 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: 1.86

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16398826).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOP53	NM_015710.5	c.118G>A	p.Gly40Ser	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.118G>A	p.Gly40Ser	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

Sep 10, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.118G>A (p.G40S) alteration is located in exon 1 (coding exon 1) of the GLTSCR2 gene. This alteration results from a G to A substitution at nucleotide position 118, causing the glycine (G) at amino acid position 40 to be replaced by a serine (S). 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	0.40
BayesDel_addAF	Benign	-0.086	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.019	T
Eigen	Benign	-0.21
Eigen_PC	Benign	-0.065
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.1	T
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-0.53	N
REVEL	Benign	0.095
Sift	Benign	0.10	T
Sift4G	Benign	0.067	T
Polyphen		0.20	B
Vest4		0.27
MutPred		0.26		Gain of phosphorylation at G40 (P = 2e-04);
MVP		0.30
MPC		0.29
ClinPred		0.39	T
GERP RS		4.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.12
gMVP		0.065

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: chr19-48248934;