Genetic Variant NM_015710.5:c.309C>G (chr19-47750197-C-G) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_015710.5(NOP53):c.309C>G(p.Thr103Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00337 in 1,611,162 control chromosomes in the GnomAD database, including 167 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.018 ( 87 hom., cov: 32)

Exomes 𝑓: 0.0018 ( 80 hom. )

Consequence

NOP53
NM_015710.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.101

Variant links:

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]

NOP53 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

BP6

Variant 19-47750197-C-G is Benign according to our data. Variant chr19-47750197-C-G is described in ClinVar as [Benign]. Clinvar id is 788027.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.101 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0604 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOP53	NM_015710.5 link	c.309C>G	p.Thr103Thr	synonymous_variant	Exon 3 of 13	ENST00000246802.10	NP_056525.2	Q9NZM5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOP53	ENST00000246802.10 link	c.309C>G	p.Thr103Thr	synonymous_variant	Exon 3 of 13	1	NM_015710.5	ENSP00000246802.4		Q9NZM5

Frequencies

GnomAD3 genomes

AF:

0.0181

AC:

2746

AN:

152104

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0625

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00766

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000176

Gnomad OTH

AF:

0.0129

GnomAD3 exomes

AF:

0.00499

AC:

1254

AN:

251422

Hom.:

AF XY:

0.00375

AC XY:

509

AN XY:

135906

show subpopulations

Gnomad AFR exome

AF:

0.0643

Gnomad AMR exome

AF:

0.00405

Gnomad ASJ exome

AF:

0.0000993

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00118

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000141

Gnomad OTH exome

AF:

0.00261

GnomAD4 exome

AF:

0.00183

AC:

2674

AN:

1458940

Hom.:

Cov.:

AF XY:

0.00168

AC XY:

1220

AN XY:

725984

show subpopulations

Gnomad4 AFR exome

AF:

0.0612

Gnomad4 AMR exome

AF:

0.00443

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00109

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000577

Gnomad4 OTH exome

AF:

0.00450

GnomAD4 genome

AF:

0.0181

AC:

2752

AN:

152222

Hom.:

Cov.:

AF XY:

0.0169

AC XY:

1256

AN XY:

74422

show subpopulations

Gnomad4 AFR

AF:

0.0624

Gnomad4 AMR

AF:

0.00765

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000176

Gnomad4 OTH

AF:

0.0137

Alfa

AF:

0.00529

Hom.:

Bravo

AF:

0.0205

Asia WGS

AF:

0.0170

AC:

AN:

3478

EpiCase

AF:

0.000164

EpiControl

AF:

0.000178

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jan 25, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

8.5

DANN

Benign

0.61

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over