rs2169480

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -1.19

Variant links:

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 links:

NUTM1 (HGNC:29919): (NUT midline carcinoma family member 1) Predicted to be located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

NUTM1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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 rank	MANE	Protein	UniProt
NUTM1	NM_001284292.2 link	c.-529A>G		upstream_gene_variant		ENST00000537011.6	NP_001271221.2	Q86Y26-4
NOP10	NM_018648.4 link	c.-95T>C		upstream_gene_variant		ENST00000328848.6	NP_061118.1	Q9NPE3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NUTM1	ENST00000537011.6 link	c.-529A>G		upstream_gene_variant		2	NM_001284292.2	ENSP00000444896.1		Q86Y26-4
NOP10	ENST00000328848.6 link	c.-95T>C		upstream_gene_variant		1	NM_018648.4	ENSP00000332198.5		Q9NPE3

Frequencies

GnomAD3 genomes

AF:

0.139

AC:

21124

AN:

152098

Hom.:

1802

Cov.:

show subpopulations

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.:

AF XY:

0.173

AC XY:

98582

AN XY:

568700

show subpopulations

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.:

AF XY:

0.136

AC XY:

10124

AN XY:

74400

show subpopulations

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

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 27, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:1

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over