3-51934706-C-T

Position:

• chr3-51934706-C-T

Variant summary

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

The NM_004704.5(RRP9):​c.1105G>A​(p.Gly369Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RRP9 NM_004704.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.72

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RRP9	NM_004704.5	c.1105G>A	p.Gly369Arg	missense_variant	12/15	ENST00000232888.7	NP_004695.1
RRP9	XM_047449172.1	c.973G>A	p.Gly325Arg	missense_variant	12/15		XP_047305128.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RRP9	ENST00000232888.7	c.1105G>A	p.Gly369Arg	missense_variant	12/15	1	NM_004704.5	ENSP00000232888.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

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

Dec 09, 2024

The c.1105G>A (p.G369R) alteration is located in exon 12 (coding exon 12) of the RRP9 gene. This alteration results from a G to A substitution at nucleotide position 1105, causing the glycine (G) at amino acid position 369 to be replaced by an arginine (R). 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	Uncertain	0.35
BayesDel_addAF	Pathogenic	0.27	D
BayesDel_noAF	Pathogenic	0.15
CADD	Uncertain	25
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.20	T
Eigen	Pathogenic	0.73
Eigen_PC	Pathogenic	0.69
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.070	D
MetaRNN	Uncertain	0.58	D
MetaSVM	Benign	-0.34	T
MutationAssessor	Uncertain	2.7	M
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-1.9	N
REVEL	Uncertain	0.30
Sift	Benign	0.075	T
Sift4G	Benign	0.13	T
Polyphen		0.99	D
Vest4		0.52
MutPred		0.38		Loss of glycosylation at P371 (P = 0.0576);
MVP		0.73
MPC		1.3
ClinPred		0.98	D
GERP RS		4.9
Varity_R		0.35
gMVP		0.56

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: chr3-51968722;