NM_018648.4:c.*45G>C

Variant names:

• chr15-34341923-C-G
• rs1045238
• NM_018648.4:c.*45G>C

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_018648.4(NOP10):​c.*45G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.165 in 1,602,948 control chromosomes in the GnomAD database, including 23,175 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.16 (2076 hom., cov: 32)
  • Exomes 𝑓: 0.17 (21099 hom.)
• Consequence: NOP10 NM_018648.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.182
• Publications: 15 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 -16 ACMG points.

• BP6: Variant 15-34341923-C-G is Benign according to our data. Variant chr15-34341923-C-G is described in ClinVar as Benign. ClinVar VariationId is 315633.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.317 is higher than 0.05.

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.*45G>C		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.*45G>C		3_prime_UTR	Exon 2 of 2	ENSP00000332198.5	Q9NPE3
	NOP10	ENST00000699935.1		c.*45G>C		3_prime_UTR	Exon 2 of 2	ENSP00000514698.1	A0A8V8TQE9
	NOP10	ENST00000699926.1		c.*45G>C		3_prime_UTR	Exon 2 of 2	ENSP00000514692.1	A0A8V8TQE5

Frequencies

GnomAD3 genomes AF: 0.162 AC: 24555 AN: 151928 Hom.: 2079 Cov.: 32

Gnomad AFR AF: 0.149

Gnomad AMI AF: 0.237

Gnomad AMR AF: 0.168

Gnomad ASJ AF: 0.173

Gnomad EAS AF: 0.330

Gnomad SAS AF: 0.228

Gnomad FIN AF: 0.0909

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.159

Gnomad OTH AF: 0.174

GnomAD2 exomes AF: 0.176 AC: 43822 AN: 248506 AF XY: 0.179

Gnomad AFR exome AF: 0.151

Gnomad AMR exome AF: 0.165

Gnomad ASJ exome AF: 0.170

Gnomad EAS exome AF: 0.319

Gnomad FIN exome AF: 0.0964

Gnomad NFE exome AF: 0.162

Gnomad OTH exome AF: 0.179

GnomAD4 exome AF: 0.166 AC: 240334 AN: 1450902 Hom.: 21099 Cov.: 30 AF XY: 0.168 AC XY: 121262 AN XY: 722192

African (AFR) AF: 0.155 AC: 5160 AN: 33248

American (AMR) AF: 0.170 AC: 7543 AN: 44436

Ashkenazi Jewish (ASJ) AF: 0.175 AC: 4546 AN: 26040

East Asian (EAS) AF: 0.303 AC: 11994 AN: 39574

South Asian (SAS) AF: 0.226 AC: 19426 AN: 85860

European-Finnish (FIN) AF: 0.0997 AC: 5317 AN: 53308

Middle Eastern (MID) AF: 0.241 AC: 1047 AN: 4340

European-Non Finnish (NFE) AF: 0.158 AC: 174887 AN: 1104162

Other (OTH) AF: 0.174 AC: 10414 AN: 59934

GnomAD4 genome AF: 0.162 AC: 24559 AN: 152046 Hom.: 2076 Cov.: 32 AF XY: 0.163 AC XY: 12135 AN XY: 74330

African (AFR) AF: 0.149 AC: 6180 AN: 41474

American (AMR) AF: 0.168 AC: 2565 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.173 AC: 598 AN: 3464

East Asian (EAS) AF: 0.330 AC: 1702 AN: 5156

South Asian (SAS) AF: 0.227 AC: 1094 AN: 4820

European-Finnish (FIN) AF: 0.0909 AC: 961 AN: 10572

Middle Eastern (MID) AF: 0.238 AC: 70 AN: 294

European-Non Finnish (NFE) AF: 0.159 AC: 10807 AN: 67976

Other (OTH) AF: 0.173 AC: 366 AN: 2114

Alfa AF: 0.159 Hom.: 374

Bravo AF: 0.168

Asia WGS AF: 0.233 AC: 812 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Dyskeratosis congenita, autosomal recessive 1 (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	19
DANN	Benign	0.78
PhyloP100		0.18
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.22		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.22		Position offset: -3

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1045238; hg19: chr15-34634124; COSMIC: COSV60995138; COSMIC: COSV60995138;