rs2169480

Positions:

• chr15-34343168-A-G

Variant summary

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

The ENST00000557912.2(NOP10):​c.-95T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.169 in 1,263,068 control chromosomes in the GnomAD database, including 20,080 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.14 (1800 hom., cov: 32)
  • Exomes 𝑓: 0.17 (18280 hom.)
• Consequence: NOP10 ENST00000557912.2 5_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -1.19

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.09).
• BP6: Variant 15-34343168-A-G is Benign according to our data. Variant chr15-34343168-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 369090.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.192 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.34343168A>G		intergenic_region
NOP10	NM_018648.4	c.-95T>C		upstream_gene_variant		ENST00000328848.6	NP_061118.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NOP10	ENST00000328848.6	c.-95T>C		upstream_gene_variant		1	NM_018648.4	ENSP00000332198.5

Frequencies

GnomAD3 genomes AF: 0.139 AC: 21124 AN: 152098 Hom.: 1802 Cov.: 32

Gnomad AFR AF: 0.0513

Gnomad AMI AF: 0.220

Gnomad AMR AF: 0.113

Gnomad ASJ AF: 0.259

Gnomad EAS AF: 0.0191

Gnomad SAS AF: 0.159

Gnomad FIN AF: 0.165

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.195

Gnomad OTH AF: 0.129

GnomAD4 exome AF: 0.173 AC: 192419 AN: 1110852 Hom.: 18280 Cov.: 15 AF XY: 0.173 AC XY: 98582 AN XY: 568700

Gnomad4 AFR exome AF: 0.0472

Gnomad4 AMR exome AF: 0.0838

Gnomad4 ASJ exome AF: 0.257

Gnomad4 EAS exome AF: 0.0115

Gnomad4 SAS exome AF: 0.163

Gnomad4 FIN exome AF: 0.161

Gnomad4 NFE exome AF: 0.190

Gnomad4 OTH exome AF: 0.169

GnomAD4 genome AF: 0.139 AC: 21120 AN: 152216 Hom.: 1800 Cov.: 32 AF XY: 0.136 AC XY: 10124 AN XY: 74400

Gnomad4 AFR AF: 0.0513

Gnomad4 AMR AF: 0.113

Gnomad4 ASJ AF: 0.259

Gnomad4 EAS AF: 0.0191

Gnomad4 SAS AF: 0.159

Gnomad4 FIN AF: 0.165

Gnomad4 NFE AF: 0.195

Gnomad4 OTH AF: 0.129

Alfa AF: 0.175 Hom.: 2511

Bravo AF: 0.127

Asia WGS AF: 0.0840 AC: 292 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 27, 2018	- -
Likely 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 26% of patients studied by a panel of primary immunodeficiencies. Number of patients: 25. Only high quality variants are reported. -

Dyskeratosis Congenita, Recessive Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.61
DANN	Benign	0.42

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: rs2169480; hg19: chr15-34635369;