Variant 1-218305111-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_016052.4(RRP15):c.489G>C(p.Gln163His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,460,666 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

RRP15
NM_016052.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.51

Variant links:

Genes affected

RRP15 (HGNC:24255): (ribosomal RNA processing 15 homolog) This gene encodes a protein that co-purifies with human nucleoli. A similar protein in budding yeast is a component of pre-60S ribosomal particles, and is required for the early maturation steps of the 60S subunit. [provided by RefSeq, Jul 2008]

RRP15 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.843

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RRP15	NM_016052.4 linkuse as main transcript	c.489G>C	p.Gln163His	missense_variant	3/5	ENST00000366932.4	NP_057136.2	Q9Y3B9
RRP15	XM_047421797.1 linkuse as main transcript	c.498G>C	p.Gln166His	missense_variant	3/5		XP_047277753.1
RRP15	XM_011509597.4 linkuse as main transcript	c.489G>C	p.Gln163His	missense_variant	3/5		XP_011507899.1
RRP15	XM_047421798.1 linkuse as main transcript	c.498G>C	p.Gln166His	missense_variant	3/5		XP_047277754.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RRP15	ENST00000366932.4 linkuse as main transcript	c.489G>C	p.Gln163His	missense_variant	3/5	1	NM_016052.4	ENSP00000355899.3		Q9Y3B9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1460666

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726690

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000270

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 25, 2024

The c.489G>C (p.Q163H) alteration is located in exon 3 (coding exon 3) of the RRP15 gene. This alteration results from a G to C substitution at nucleotide position 489, causing the glutamine (Q) at amino acid position 163 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.92

BayesDel_addAF

Uncertain

0.14

BayesDel_noAF

Uncertain

-0.040

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.13

Eigen

Pathogenic

0.90

Eigen_PC

Pathogenic

0.91

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.93

M_CAP

Benign

0.022

MetaRNN

Pathogenic

0.84

MetaSVM

Benign

-0.60

MutationAssessor

Pathogenic

3.0

PrimateAI

Uncertain

0.69

PROVEAN

Uncertain

-3.9

REVEL

Uncertain

0.47

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.019

Polyphen

1.0

Vest4

0.77

MutPred

0.49

Loss of disorder (P = 0.0837);

MVP

0.76

MPC

0.35

ClinPred

1.0

GERP RS

6.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.94

gMVP

0.43

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over