15-34341923-C-G

Position:

chr15-34341923-C-G

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_018648.4(NOP10):c.*45G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.165 in 1,602,948 control chromosomes in the GnomAD database, including 23,175 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.16 ( 2076 hom., cov: 32)

Exomes 𝑓: 0.17 ( 21099 hom. )

Consequence

NOP10
NM_018648.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.182

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 15-34341923-C-G is Benign according to our data. Variant chr15-34341923-C-G is described in ClinVar as [Benign]. Clinvar id is 315633.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.317 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.*45G>C		3_prime_UTR_variant	2/2	ENST00000328848.6	NP_061118.1	Q9NPE3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NOP10	ENST00000328848 linkuse as main transcript	c.*45G>C		3_prime_UTR_variant	2/2	1	NM_018648.4	ENSP00000332198.5		Q9NPE3

Frequencies

GnomAD3 genomes

AF:

0.162

AC:

24555

AN:

151928

Hom.:

2079

Cov.:

show subpopulations

Gnomad AFR

AF:

0.149

Gnomad AMI

AF:

0.237

Gnomad AMR

AF:

0.168

Gnomad ASJ

AF:

0.173

Gnomad EAS

AF:

0.330

Gnomad SAS

AF:

0.228

Gnomad FIN

AF:

0.0909

Gnomad MID

AF:

0.244

Gnomad NFE

AF:

0.159

Gnomad OTH

AF:

0.174

GnomAD3 exomes

AF:

0.176

AC:

43822

AN:

248506

Hom.:

4147

AF XY:

0.179

AC XY:

24045

AN XY:

134460

show subpopulations

Gnomad AFR exome

AF:

0.151

Gnomad AMR exome

AF:

0.165

Gnomad ASJ exome

AF:

0.170

Gnomad EAS exome

AF:

0.319

Gnomad SAS exome

AF:

0.227

Gnomad FIN exome

AF:

0.0964

Gnomad NFE exome

AF:

0.162

Gnomad OTH exome

AF:

0.179

GnomAD4 exome

AF:

0.166

AC:

240334

AN:

1450902

Hom.:

21099

Cov.:

AF XY:

0.168

AC XY:

121262

AN XY:

722192

show subpopulations

Gnomad4 AFR exome

AF:

0.155

Gnomad4 AMR exome

AF:

0.170

Gnomad4 ASJ exome

AF:

0.175

Gnomad4 EAS exome

AF:

0.303

Gnomad4 SAS exome

AF:

0.226

Gnomad4 FIN exome

AF:

0.0997

Gnomad4 NFE exome

AF:

0.158

Gnomad4 OTH exome

AF:

0.174

GnomAD4 genome

AF:

0.162

AC:

24559

AN:

152046

Hom.:

2076

Cov.:

AF XY:

0.163

AC XY:

12135

AN XY:

74330

show subpopulations

Gnomad4 AFR

AF:

0.149

Gnomad4 AMR

AF:

0.168

Gnomad4 ASJ

AF:

0.173

Gnomad4 EAS

AF:

0.330

Gnomad4 SAS

AF:

0.227

Gnomad4 FIN

AF:

0.0909

Gnomad4 NFE

AF:

0.159

Gnomad4 OTH

AF:

0.173

Alfa

AF:

0.159

Hom.:

374

Bravo

AF:

0.168

Asia WGS

AF:

0.233

AC:

812

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

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	-	- -

not specified

Benign:1

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 34% of patients studied by a panel of primary immunodeficiencies. Number of patients: 32. Only high quality variants are reported. -

Dyskeratosis congenita, autosomal recessive 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

DANN

Benign

0.78

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.0

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.22

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.22

Position offset: -3

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