rs422388

Variant names:

• chr15-34342123-C-G
• rs422388
• NM_018648.4:c.55-15G>C

Your query was ambiguous. Multiple possible variants found:

• chr15-34342123-C-G
• chr15-34342123-C-A
• chr15-34342123-C-T

Variant summary

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

The NM_018648.4(NOP10):​c.55-15G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.368 in 1,611,796 control chromosomes in the GnomAD database, including 113,627 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.43 (15600 hom., cov: 31)
  • Exomes 𝑓: 0.36 (98027 hom.)
• Consequence: NOP10 NM_018648.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:12
• Conservation: PhyloP100: 0.0690
• Publications: 13 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: Ambry Genetics, G2P, 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: AD, Unknown Classification: LIMITED Submitted by: ClinGen, Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 15-34342123-C-G is Benign according to our data. Variant chr15-34342123-C-G is described in ClinVar as Benign. ClinVar VariationId is 261036.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.649 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.55-15G>C		intron	N/A	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.55-15G>C		intron	N/A	ENSP00000332198.5	Q9NPE3
	NOP10	ENST00000699935.1		c.64G>C	p.Val22Leu	missense	Exon 2 of 2	ENSP00000514698.1	A0A8V8TQE9
	NOP10	ENST00000699926.1		c.55-12G>C		intron	N/A	ENSP00000514692.1	A0A8V8TQE5

Frequencies

GnomAD3 genomes AF: 0.431 AC: 65349 AN: 151738 Hom.: 15570 Cov.: 31

Gnomad AFR AF: 0.655

Gnomad AMI AF: 0.456

Gnomad AMR AF: 0.327

Gnomad ASJ AF: 0.438

Gnomad EAS AF: 0.349

Gnomad SAS AF: 0.389

Gnomad FIN AF: 0.254

Gnomad MID AF: 0.440

Gnomad NFE AF: 0.355

Gnomad OTH AF: 0.402

GnomAD2 exomes AF: 0.359 AC: 90225 AN: 251032 AF XY: 0.358

Gnomad AFR exome AF: 0.662

Gnomad AMR exome AF: 0.267

Gnomad ASJ exome AF: 0.449

Gnomad EAS exome AF: 0.338

Gnomad FIN exome AF: 0.251

Gnomad NFE exome AF: 0.352

Gnomad OTH exome AF: 0.359

GnomAD4 exome AF: 0.361 AC: 527411 AN: 1459940 Hom.: 98027 Cov.: 34 AF XY: 0.361 AC XY: 262471 AN XY: 726312

African (AFR) AF: 0.680 AC: 22738 AN: 33436

American (AMR) AF: 0.279 AC: 12475 AN: 44696

Ashkenazi Jewish (ASJ) AF: 0.442 AC: 11555 AN: 26126

East Asian (EAS) AF: 0.315 AC: 12516 AN: 39686

South Asian (SAS) AF: 0.393 AC: 33850 AN: 86200

European-Finnish (FIN) AF: 0.260 AC: 13867 AN: 53406

Middle Eastern (MID) AF: 0.470 AC: 2708 AN: 5766

European-Non Finnish (NFE) AF: 0.355 AC: 394693 AN: 1110298

Other (OTH) AF: 0.381 AC: 23009 AN: 60326

GnomAD4 genome AF: 0.431 AC: 65427 AN: 151856 Hom.: 15600 Cov.: 31 AF XY: 0.423 AC XY: 31408 AN XY: 74196

African (AFR) AF: 0.655 AC: 27097 AN: 41362

American (AMR) AF: 0.327 AC: 4989 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.438 AC: 1521 AN: 3470

East Asian (EAS) AF: 0.349 AC: 1800 AN: 5160

South Asian (SAS) AF: 0.388 AC: 1868 AN: 4816

European-Finnish (FIN) AF: 0.254 AC: 2675 AN: 10526

Middle Eastern (MID) AF: 0.432 AC: 127 AN: 294

European-Non Finnish (NFE) AF: 0.355 AC: 24095 AN: 67944

Other (OTH) AF: 0.399 AC: 842 AN: 2108

Alfa AF: 0.396 Hom.: 2253

Bravo AF: 0.443

Asia WGS AF: 0.354 AC: 1232 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	5	not specified (5)
-	-	3	Dyskeratosis congenita, autosomal recessive 1 (3)
-	-	3	not provided (3)
-	-	1	Dyskeratosis congenita (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.92
DANN	Benign	0.64
PhyloP100		0.069
Mutation Taster		=100/0	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs422388;

hg19: chr15-34634324;

COSMIC: COSV60995160;

COSMIC: COSV60995160;