15-34341938-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_018648.4(NOP10):c.*30A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.166 in 1,608,988 control chromosomes in the GnomAD database, including 23,408 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.16 (2039 hom., cov: 32)
  • Exomes 𝑓: 0.17 (21369 hom.)
• Consequence: NOP10 NM_018648.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -2.40

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 15-34341938-T-C is Benign according to our data. Variant chr15-34341938-T-C is described in ClinVar as [Benign]. Clinvar id is 315636.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-34341938-T-C is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.314 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NOP10	NM_018648.4	c.*30A>G		3_prime_UTR_variant	2/2	ENST00000328848.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NOP10	ENST00000328848.6	c.*30A>G		3_prime_UTR_variant	2/2	1	NM_018648.4	P4

Frequencies

GnomAD3 genomes AF: 0.161 AC: 24467 AN: 151876 Hom.: 2042 Cov.: 32

Gnomad AFR AF: 0.148

Gnomad AMI AF: 0.233

Gnomad AMR AF: 0.168

Gnomad ASJ AF: 0.172

Gnomad EAS AF: 0.327

Gnomad SAS AF: 0.227

Gnomad FIN AF: 0.0905

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.159

Gnomad OTH AF: 0.173

GnomAD3 exomes AF: 0.176 AC: 44166 AN: 250296 Hom.: 4140 AF XY: 0.179 AC XY: 24219 AN XY: 135354

Gnomad AFR exome AF: 0.152

Gnomad AMR exome AF: 0.165

Gnomad ASJ exome AF: 0.171

Gnomad EAS exome AF: 0.318

Gnomad SAS exome AF: 0.227

Gnomad FIN exome AF: 0.0962

Gnomad NFE exome AF: 0.162

Gnomad OTH exome AF: 0.180

GnomAD4 exome AF: 0.167 AC: 242751 AN: 1456994 Hom.: 21369 Cov.: 31 AF XY: 0.169 AC XY: 122376 AN XY: 724974

Gnomad4 AFR exome AF: 0.156

Gnomad4 AMR exome AF: 0.170

Gnomad4 ASJ exome AF: 0.175

Gnomad4 EAS exome AF: 0.303

Gnomad4 SAS exome AF: 0.227

Gnomad4 FIN exome AF: 0.0997

Gnomad4 NFE exome AF: 0.160

Gnomad4 OTH exome AF: 0.174

GnomAD4 genome AF: 0.161 AC: 24471 AN: 151994 Hom.: 2039 Cov.: 32 AF XY: 0.163 AC XY: 12081 AN XY: 74292

Gnomad4 AFR AF: 0.148

Gnomad4 AMR AF: 0.168

Gnomad4 ASJ AF: 0.172

Gnomad4 EAS AF: 0.327

Gnomad4 SAS AF: 0.226

Gnomad4 FIN AF: 0.0905

Gnomad4 NFE AF: 0.159

Gnomad4 OTH AF: 0.173

Alfa AF: 0.153 Hom.: 373

Bravo AF: 0.168

Asia WGS AF: 0.233 AC: 811 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

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 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:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Apr 03, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.73
Dann	Benign	0.38
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.0

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

Other links and lift over

dbSNP: rs1045194; hg19: chr15-34634139; COSMIC: COSV60995151; COSMIC: COSV60995151;