15-34341819-C-T

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.*149G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0975 in 803,520 control chromosomes in the GnomAD database, including 4,838 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.081 (719 hom., cov: 32)
  • Exomes 𝑓: 0.10 (4119 hom.)
• Consequence: NOP10 NM_018648.4 3_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.0150

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=-0.8).
• BP6: Variant 15-34341819-C-T is Benign according to our data. Variant chr15-34341819-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 315630.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-34341819-C-T is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0998 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NOP10	NM_018648.4	c.*149G>A		3_prime_UTR_variant	2/2	ENST00000328848.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NOP10	ENST00000328848.6	c.*149G>A		3_prime_UTR_variant	2/2	1	NM_018648.4	P4

Frequencies

GnomAD3 genomes AF: 0.0814 AC: 12364 AN: 151984 Hom.: 718 Cov.: 32

Gnomad AFR AF: 0.0182

Gnomad AMI AF: 0.0614

Gnomad AMR AF: 0.0642

Gnomad ASJ AF: 0.105

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.105

Gnomad FIN AF: 0.242

Gnomad MID AF: 0.102

Gnomad NFE AF: 0.102

Gnomad OTH AF: 0.0892

GnomAD4 exome AF: 0.101 AC: 66013 AN: 651418 Hom.: 4119 Cov.: 8 AF XY: 0.103 AC XY: 35327 AN XY: 344584

Gnomad4 AFR exome AF: 0.0149

Gnomad4 AMR exome AF: 0.0559

Gnomad4 ASJ exome AF: 0.108

Gnomad4 EAS exome AF: 0.000124

Gnomad4 SAS exome AF: 0.115

Gnomad4 FIN exome AF: 0.228

Gnomad4 NFE exome AF: 0.102

Gnomad4 OTH exome AF: 0.0932

GnomAD4 genome AF: 0.0813 AC: 12364 AN: 152102 Hom.: 719 Cov.: 32 AF XY: 0.0880 AC XY: 6542 AN XY: 74334

Gnomad4 AFR AF: 0.0181

Gnomad4 AMR AF: 0.0641

Gnomad4 ASJ AF: 0.105

Gnomad4 EAS AF: 0.00135

Gnomad4 SAS AF: 0.105

Gnomad4 FIN AF: 0.242

Gnomad4 NFE AF: 0.102

Gnomad4 OTH AF: 0.0878

Alfa AF: 0.0891 Hom.: 718

Bravo AF: 0.0647

Asia WGS AF: 0.0410 AC: 141 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

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

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 27, 2018

- -

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	-0.80
Cadd	Benign	7.9
Dann	Benign	0.80

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: rs7173; hg19: chr15-34634020;