chr15-34341832-A-G

Position:

• chr15-34341832-A-G

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.*136T>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 0.159 in 890,382 control chromosomes in the GnomAD database, including 12,372 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.16 (2075 hom., cov: 32)
  • Exomes 𝑓: 0.16 (10297 hom.)
• Consequence: NOP10 NM_018648.4 3_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.252

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 15-34341832-A-G is Benign according to our data. Variant chr15-34341832-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 315631.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-34341832-A-G is described in Lovd as [Benign].
• 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	c.*136T>C		3_prime_UTR_variant	2/2	ENST00000328848.6	NP_061118.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NOP10	ENST00000328848	c.*136T>C		3_prime_UTR_variant	2/2	1	NM_018648.4	ENSP00000332198.5

Frequencies

GnomAD3 genomes AF: 0.162 AC: 24570 AN: 152086 Hom.: 2078 Cov.: 32

Gnomad AFR AF: 0.149

Gnomad AMI AF: 0.237

Gnomad AMR AF: 0.168

Gnomad ASJ AF: 0.172

Gnomad EAS AF: 0.330

Gnomad SAS AF: 0.227

Gnomad FIN AF: 0.0906

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.159

Gnomad OTH AF: 0.174

GnomAD4 exome AF: 0.159 AC: 117390 AN: 738178 Hom.: 10297 Cov.: 10 AF XY: 0.163 AC XY: 63120 AN XY: 387474

Gnomad4 AFR exome AF: 0.152

Gnomad4 AMR exome AF: 0.172

Gnomad4 ASJ exome AF: 0.173

Gnomad4 EAS exome AF: 0.300

Gnomad4 SAS exome AF: 0.225

Gnomad4 FIN exome AF: 0.0995

Gnomad4 NFE exome AF: 0.144

Gnomad4 OTH exome AF: 0.165

GnomAD4 genome AF: 0.161 AC: 24574 AN: 152204 Hom.: 2075 Cov.: 32 AF XY: 0.163 AC XY: 12141 AN XY: 74422

Gnomad4 AFR AF: 0.149

Gnomad4 AMR AF: 0.167

Gnomad4 ASJ AF: 0.172

Gnomad4 EAS AF: 0.330

Gnomad4 SAS AF: 0.226

Gnomad4 FIN AF: 0.0906

Gnomad4 NFE AF: 0.159

Gnomad4 OTH AF: 0.174

Alfa AF: 0.0594 Hom.: 53

Bravo AF: 0.168

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

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

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. -

Agenesis of the corpus callosum with peripheral neuropathy Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Dyskeratosis Congenita, Recessive Benign:1

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	-0.89
CADD	Benign	6.9
DANN	Benign	0.61
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		0.97

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: rs3063; hg19: chr15-34634033; COSMIC: COSV60995282; COSMIC: COSV60995282;