rs2169480

Variant names:

• chr15-34343168-A-G
• rs2169480
• ENST00000699926.1:c.-95T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000699926.1(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 ENST00000699926.1 5_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -1.19
• Publications: 8 publications found

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]

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]

ACMG classification

Our verdict: Benign. The variant received -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 Benign/Likely_benign. ClinVar VariationId 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	c.-529A>G		upstream_gene_variant		ENST00000537011.6	NP_001271221.2
NOP10	NM_018648.4	c.-95T>C		upstream_gene_variant		ENST00000328848.6	NP_061118.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NUTM1	ENST00000537011.6	c.-529A>G		upstream_gene_variant		2	NM_001284292.2	ENSP00000444896.1
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

African (AFR) AF: 0.0472 AC: 1262 AN: 26742

American (AMR) AF: 0.0838 AC: 3674 AN: 43830

Ashkenazi Jewish (ASJ) AF: 0.257 AC: 6142 AN: 23860

East Asian (EAS) AF: 0.0115 AC: 437 AN: 38160

South Asian (SAS) AF: 0.163 AC: 12886 AN: 79042

European-Finnish (FIN) AF: 0.161 AC: 8555 AN: 53092

Middle Eastern (MID) AF: 0.184 AC: 925 AN: 5024

European-Non Finnish (NFE) AF: 0.190 AC: 150315 AN: 792360

Other (OTH) AF: 0.169 AC: 8223 AN: 48742

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

African (AFR) AF: 0.0513 AC: 2129 AN: 41536

American (AMR) AF: 0.113 AC: 1730 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.259 AC: 898 AN: 3468

East Asian (EAS) AF: 0.0191 AC: 99 AN: 5184

South Asian (SAS) AF: 0.159 AC: 768 AN: 4826

European-Finnish (FIN) AF: 0.165 AC: 1748 AN: 10594

Middle Eastern (MID) AF: 0.170 AC: 50 AN: 294

European-Non Finnish (NFE) AF: 0.195 AC: 13225 AN: 67992

Other (OTH) AF: 0.129 AC: 272 AN: 2116

Alfa AF: 0.170 Hom.: 3062

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

-

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
PhyloP100		-1.2
PromoterAI		0.18	Neutral
Mutation Taster		=300/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2169480; hg19: chr15-34635369;