Variant 1-218302557-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_016052.4(RRP15):c.403C>A(p.Gln135Lys) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000548 in 1,458,622 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

RRP15
NM_016052.4 missense, splice_region

Scores

Splicing: ADA: 0.1784

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.21

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:

RRP15 (HGNC:):

RRP15 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.13419664).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RRP15	NM_016052.4 linkuse as main transcript	c.403C>A	p.Gln135Lys	missense_variant, splice_region_variant	2/5	ENST00000366932.4	NP_057136.2	Q9Y3B9
RRP15	XM_047421797.1 linkuse as main transcript	c.412C>A	p.Gln138Lys	missense_variant, splice_region_variant	2/5		XP_047277753.1
RRP15	XM_011509597.4 linkuse as main transcript	c.403C>A	p.Gln135Lys	missense_variant, splice_region_variant	2/5		XP_011507899.1
RRP15	XM_047421798.1 linkuse as main transcript	c.412C>A	p.Gln138Lys	missense_variant, splice_region_variant	2/5		XP_047277754.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RRP15	ENST00000366932.4 linkuse as main transcript	c.403C>A	p.Gln135Lys	missense_variant, splice_region_variant	2/5	1	NM_016052.4	ENSP00000355899.3		Q9Y3B9
RRP15	ENST00000491428.1 linkuse as main transcript	n.378C>A		non_coding_transcript_exon_variant	2/2	1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000548

AC:

AN:

1458622

Hom.:

Cov.:

AF XY:

0.00000689

AC XY:

AN XY:

725732

show subpopulations

Gnomad4 AFR exome

AF:

0.0000302

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:

0.00000540

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000370

Hom.:

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

Oct 08, 2024

The c.403C>A (p.Q135K) alteration is located in exon 2 (coding exon 2) of the RRP15 gene. This alteration results from a C to A substitution at nucleotide position 403, causing the glutamine (Q) at amino acid position 135 to be replaced by a lysine (K). 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

Benign

0.12

BayesDel_addAF

Benign

-0.066

BayesDel_noAF

Benign

-0.33

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.0065

Eigen

Benign

-0.28

Eigen_PC

Benign

-0.10

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.69

M_CAP

Benign

0.011

MetaRNN

Benign

0.13

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.3

PrimateAI

Benign

0.36

PROVEAN

Benign

-1.3

REVEL

Benign

0.14

Sift

Benign

0.21

Sift4G

Benign

0.38

Polyphen

0.29

Vest4

0.11

MVP

0.47

MPC

0.12

ClinPred

0.85

GERP RS

5.0

Varity_R

0.36

gMVP

0.16

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.18

dbscSNV1_RF

Benign

0.30

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over