rs115413508

Variant names:

• chr15-34341839-C-T
• rs115413508
• NM_018648.4:c.*129G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_018648.4(NOP10):​c.*129G>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 0.00259 in 936,098 control chromosomes in the GnomAD database, including 30 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0091 (14 hom., cov: 32)
  • Exomes 𝑓: 0.0013 (16 hom.)
• Consequence: NOP10 NM_018648.4 3_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.356
• Publications: 2 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]

NOP10 Gene-Disease associations (from GenCC):

• dyskeratosis congenita, autosomal recessive 1

  Inheritance: AR Classification: STRONG, MODERATE, LIMITED Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• dyskeratosis congenita

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• pulmonary fibrosis and/or bone marrow failure syndrome, telomere-related, 9

  Inheritance: Unknown, AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), ClinGen

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 15-34341839-C-T is Benign according to our data. Variant chr15-34341839-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 315632.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00909 (1384/152258) while in subpopulation AFR AF = 0.0304 (1262/41524). AF 95% confidence interval is 0.029. There are 14 homozygotes in GnomAd4. There are 655 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 14 AR,Unknown,AD gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018648.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOP10	NM_018648.4	MANE Select	c.*129G>A		3_prime_UTR	Exon 2 of 2	NP_061118.1	Q9NPE3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOP10	ENST00000328848.6	TSL:1 MANE Select	c.*129G>A		3_prime_UTR	Exon 2 of 2	ENSP00000332198.5	Q9NPE3
	NOP10	ENST00000699935.1		c.*129G>A		3_prime_UTR	Exon 2 of 2	ENSP00000514698.1	A0A8V8TQE9
	NOP10	ENST00000699926.1		c.*129G>A		3_prime_UTR	Exon 2 of 2	ENSP00000514692.1	A0A8V8TQE5

Frequencies

GnomAD3 genomes AF: 0.00905 AC: 1377 AN: 152140 Hom.: 15 Cov.: 32

Gnomad AFR AF: 0.0303

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00465

Gnomad ASJ AF: 0.00403

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000279

Gnomad OTH AF: 0.00860

GnomAD4 exome AF: 0.00133 AC: 1045 AN: 783840 Hom.: 16 Cov.: 11 AF XY: 0.00116 AC XY: 475 AN XY: 409280

African (AFR) AF: 0.0295 AC: 588 AN: 19908

American (AMR) AF: 0.00228 AC: 80 AN: 35096

Ashkenazi Jewish (ASJ) AF: 0.00507 AC: 108 AN: 21312

East Asian (EAS) AF: 0.00 AC: 0 AN: 33004

South Asian (SAS) AF: 0.000105 AC: 7 AN: 66792

European-Finnish (FIN) AF: 0.0000666 AC: 3 AN: 45018

Middle Eastern (MID) AF: 0.00316 AC: 9 AN: 2846

European-Non Finnish (NFE) AF: 0.000220 AC: 115 AN: 521966

Other (OTH) AF: 0.00356 AC: 135 AN: 37898

GnomAD4 genome AF: 0.00909 AC: 1384 AN: 152258 Hom.: 14 Cov.: 32 AF XY: 0.00880 AC XY: 655 AN XY: 74452

African (AFR) AF: 0.0304 AC: 1262 AN: 41524

American (AMR) AF: 0.00464 AC: 71 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00403 AC: 14 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10604

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000279 AC: 19 AN: 68024

Other (OTH) AF: 0.00851 AC: 18 AN: 2116

Alfa AF: 0.00512 Hom.: 10

Bravo AF: 0.0102

Asia WGS AF: 0.00375 AC: 13 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Agenesis of the corpus callosum with peripheral neuropathy (1)
-	-	1	Dyskeratosis congenita, autosomal recessive 1 (1)
-	-	1	Dyskeratosis Congenita, Recessive (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	5.9
DANN	Benign	0.49
PhyloP100		-0.36
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism

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: rs115413508; hg19: chr15-34634040;