chr15-34342123-C-G

Position:

chr15-34342123-C-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_018648.4(NOP10):c.55-15G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.368 in 1,611,796 control chromosomes in the GnomAD database, including 113,627 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.43 ( 15600 hom., cov: 31)

Exomes 𝑓: 0.36 ( 98027 hom. )

Consequence

NOP10
NM_018648.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: 0.0690

Variant links:

Genes affected

NOP10 (HGNC:14378): (NOP10 ribonucleoprotein) This gene is a member of the H/ACA snoRNPs (small nucleolar ribonucleoproteins) gene family. snoRNPs are involved in various aspects of rRNA processing and modification and have been classified into two families: C/D and H/ACA. The H/ACA snoRNPs also include the DKC1, NOLA1 and NOLA2 proteins. These four H/ACA snoRNP proteins localize to the dense fibrillar components of nucleoli and to coiled (Cajal) bodies in the nucleus. Both 18S rRNA production and rRNA pseudouridylation are impaired if any one of the four proteins is depleted. The four H/ACA snoRNP proteins are also components of the telomerase complex. This gene encodes a protein related to Saccharomyces cerevisiae Nop10p. [provided by RefSeq, Jul 2008]

NOP10 links:

NOP10 (HGNC:):

NOP10 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 15-34342123-C-G is Benign according to our data. Variant chr15-34342123-C-G is described in ClinVar as [Benign]. Clinvar id is 261036.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-34342123-C-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.649 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NOP10	NM_018648.4 linkuse as main transcript	c.55-15G>C		intron_variant		ENST00000328848.6	NP_061118.1	Q9NPE3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NOP10	ENST00000328848.6 linkuse as main transcript	c.55-15G>C		intron_variant		1	NM_018648.4	ENSP00000332198.5		Q9NPE3

Frequencies

GnomAD3 genomes

AF:

0.431

AC:

65349

AN:

151738

Hom.:

15570

Cov.:

show subpopulations

Gnomad AFR

AF:

0.655

Gnomad AMI

AF:

0.456

Gnomad AMR

AF:

0.327

Gnomad ASJ

AF:

0.438

Gnomad EAS

AF:

0.349

Gnomad SAS

AF:

0.389

Gnomad FIN

AF:

0.254

Gnomad MID

AF:

0.440

Gnomad NFE

AF:

0.355

Gnomad OTH

AF:

0.402

GnomAD3 exomes

AF:

0.359

AC:

90225

AN:

251032

Hom.:

17391

AF XY:

0.358

AC XY:

48538

AN XY:

135662

show subpopulations

Gnomad AFR exome

AF:

0.662

Gnomad AMR exome

AF:

0.267

Gnomad ASJ exome

AF:

0.449

Gnomad EAS exome

AF:

0.338

Gnomad SAS exome

AF:

0.392

Gnomad FIN exome

AF:

0.251

Gnomad NFE exome

AF:

0.352

Gnomad OTH exome

AF:

0.359

GnomAD4 exome

AF:

0.361

AC:

527411

AN:

1459940

Hom.:

98027

Cov.:

AF XY:

0.361

AC XY:

262471

AN XY:

726312

show subpopulations

Gnomad4 AFR exome

AF:

0.680

Gnomad4 AMR exome

AF:

0.279

Gnomad4 ASJ exome

AF:

0.442

Gnomad4 EAS exome

AF:

0.315

Gnomad4 SAS exome

AF:

0.393

Gnomad4 FIN exome

AF:

0.260

Gnomad4 NFE exome

AF:

0.355

Gnomad4 OTH exome

AF:

0.381

GnomAD4 genome

AF:

0.431

AC:

65427

AN:

151856

Hom.:

15600

Cov.:

AF XY:

0.423

AC XY:

31408

AN XY:

74196

show subpopulations

Gnomad4 AFR

AF:

0.655

Gnomad4 AMR

AF:

0.327

Gnomad4 ASJ

AF:

0.438

Gnomad4 EAS

AF:

0.349

Gnomad4 SAS

AF:

0.388

Gnomad4 FIN

AF:

0.254

Gnomad4 NFE

AF:

0.355

Gnomad4 OTH

AF:

0.399

Alfa

AF:

0.396

Hom.:

2253

Bravo

AF:

0.443

Asia WGS

AF:

0.354

AC:

1232

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Benign, criteria provided, single submitter	clinical testing	Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan	Jan 24, 2024	This variant is classified as Benign based on local population frequency. This variant was detected in 59% of patients studied by a panel of primary immunodeficiencies. Number of patients: 56. Only high quality variants are reported. -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 29, 2016	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Dyskeratosis congenita, autosomal recessive 1

Benign:3

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Sep 05, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Dyskeratosis congenita

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 24, 2014

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.92

DANN

Benign

0.64

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