chr3-51938103-C-A

Position:

• chr3-51938103-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004704.5(RRP9):​c.272G>T​(p.Arg91Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000207 in 1,447,338 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: RRP9 NM_004704.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.55

Genes affected

RRP9 (HGNC:16829): (ribosomal RNA processing 9, U3 small nucleolar RNA binding protein) This gene encodes a member of the WD-repeat protein family. The encoded protein is a component of the nucleolar small nuclear ribonucleoprotein particle (snoRNP) and is essential for 18s rRNA processing during ribosome synthesis. It contains seven WD domains required for nucleolar localization and specific interaction with the U3 small nucleolar RNA (U3 snoRNA). [provided by RefSeq, Oct 2012]

ACMG classification

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=0.196715).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RRP9	NM_004704.5	c.272G>T	p.Arg91Leu	missense_variant	3/15	ENST00000232888.7
RRP9	XM_047449172.1	c.140G>T	p.Arg47Leu	missense_variant	3/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RRP9	ENST00000232888.7	c.272G>T	p.Arg91Leu	missense_variant	3/15	1	NM_004704.5	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000207 AC: 3 AN: 1447338 Hom.: 0 Cov.: 31 AF XY: 0.00000139 AC XY: 1 AN XY: 720200

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: 0.00

Gnomad4 OTH exome AF: 0.0000501

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 23, 2024

The c.272G>T (p.R91L) alteration is located in exon 3 (coding exon 3) of the RRP9 gene. This alteration results from a G to T substitution at nucleotide position 272, causing the arginine (R) at amino acid position 91 to be replaced by a leucine (L). 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	0.28
BayesDel_addAF	Benign	-0.055	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.24	T
Eigen	Benign	-0.28
Eigen_PC	Benign	-0.26
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.037	D
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-0.89	T
MutationAssessor	Uncertain	2.5	M
MutationTaster	Benign	0.66	D
PrimateAI	Uncertain	0.49	T
PROVEAN	Uncertain	-3.4	D
REVEL	Benign	0.067
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.019	D
Polyphen		0.45	B
Vest4		0.36
MutPred		0.41		Loss of MoRF binding (P = 0.0262);
MVP		0.58
MPC		0.90
ClinPred		0.98	D
GERP RS		2.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.30
gMVP		0.16

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-51972119;