15-34341926-A-AG

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP6 BS2

The NM_018648.4(NOP10):c.*41_*42insC variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00741 in 1,609,704 control chromosomes in the GnomAD database, including 64 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.0051 (5 hom., cov: 32)
  • Exomes 𝑓: 0.0076 (59 hom.)
• Consequence: NOP10 NM_018648.4 3_prime_UTR
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:1
• Conservation: PhyloP100: 0.0120

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 Likely_benign. Variant got -5 ACMG points.

• BP6: Variant 15-34341926-A-AG is Benign according to our data. Variant chr15-34341926-A-AG is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 315634.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.
• BS2: High Homozygotes in GnomAd at 5 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NOP10	NM_018648.4	c.*41_*42insC		3_prime_UTR_variant	2/2	ENST00000328848.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NOP10	ENST00000328848.6	c.*41_*42insC		3_prime_UTR_variant	2/2	1	NM_018648.4	P4

Frequencies

GnomAD3 genomes AF: 0.00513 AC: 781 AN: 152140 Hom.: 5 Cov.: 32

Gnomad AFR AF: 0.00167

Gnomad AMI AF: 0.00987

Gnomad AMR AF: 0.00124

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00830

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00867

Gnomad OTH AF: 0.00191

GnomAD3 exomes AF: 0.00542 AC: 1356 AN: 250332 Hom.: 8 AF XY: 0.00537 AC XY: 727 AN XY: 135440

Gnomad AFR exome AF: 0.00186

Gnomad AMR exome AF: 0.000958

Gnomad ASJ exome AF: 0.000398

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00115

Gnomad FIN exome AF: 0.0110

Gnomad NFE exome AF: 0.00874

Gnomad OTH exome AF: 0.00458

GnomAD4 exome AF: 0.00765 AC: 11148 AN: 1457446 Hom.: 59 Cov.: 30 AF XY: 0.00747 AC XY: 5419 AN XY: 725240

Gnomad4 AFR exome AF: 0.00111

Gnomad4 AMR exome AF: 0.00123

Gnomad4 ASJ exome AF: 0.000728

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00121

Gnomad4 FIN exome AF: 0.00952

Gnomad4 NFE exome AF: 0.00903

Gnomad4 OTH exome AF: 0.00666

GnomAD4 genome AF: 0.00514 AC: 782 AN: 152258 Hom.: 5 Cov.: 32 AF XY: 0.00480 AC XY: 357 AN XY: 74438

Gnomad4 AFR AF: 0.00166

Gnomad4 AMR AF: 0.00124

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000622

Gnomad4 FIN AF: 0.00830

Gnomad4 NFE AF: 0.00867

Gnomad4 OTH AF: 0.00189

Alfa AF: 0.00666 Hom.: 2

Bravo AF: 0.00467

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1 Benign:1

Revision: criteria provided, conflicting classifications

Submissions by phenotype

Dyskeratosis Congenita, Recessive Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 10, 2019

- -

Computational scores

Source: dbNSFP v4.3

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: rs528879821; hg19: chr15-34634127;