chr3-51941561-C-T

Position:

• chr3-51941561-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004704.5(RRP9):​c.88-70G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.22 in 1,387,700 control chromosomes in the GnomAD database, including 40,614 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.28 (6662 hom., cov: 33)
  • Exomes 𝑓: 0.21 (33952 hom.)
• Consequence: RRP9 NM_004704.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.418

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.393 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RRP9	NM_004704.5	c.88-70G>A		intron_variant		ENST00000232888.7	NP_004695.1
RRP9	XM_047449172.1	c.-61-54G>A		intron_variant			XP_047305128.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RRP9	ENST00000232888.7	c.88-70G>A		intron_variant		1	NM_004704.5	ENSP00000232888.6

Frequencies

GnomAD3 genomes AF: 0.278 AC: 42154 AN: 151850 Hom.: 6653 Cov.: 33

Gnomad AFR AF: 0.392

Gnomad AMI AF: 0.125

Gnomad AMR AF: 0.401

Gnomad ASJ AF: 0.263

Gnomad EAS AF: 0.407

Gnomad SAS AF: 0.162

Gnomad FIN AF: 0.169

Gnomad MID AF: 0.287

Gnomad NFE AF: 0.198

Gnomad OTH AF: 0.284

GnomAD4 exome AF: 0.213 AC: 263587 AN: 1235736 Hom.: 33952 Cov.: 17 AF XY: 0.210 AC XY: 130906 AN XY: 623644

Gnomad4 AFR exome AF: 0.405

Gnomad4 AMR exome AF: 0.517

Gnomad4 ASJ exome AF: 0.268

Gnomad4 EAS exome AF: 0.451

Gnomad4 SAS exome AF: 0.154

Gnomad4 FIN exome AF: 0.173

Gnomad4 NFE exome AF: 0.188

Gnomad4 OTH exome AF: 0.224

GnomAD4 genome AF: 0.278 AC: 42192 AN: 151964 Hom.: 6662 Cov.: 33 AF XY: 0.278 AC XY: 20683 AN XY: 74296

Gnomad4 AFR AF: 0.391

Gnomad4 AMR AF: 0.402

Gnomad4 ASJ AF: 0.263

Gnomad4 EAS AF: 0.407

Gnomad4 SAS AF: 0.162

Gnomad4 FIN AF: 0.169

Gnomad4 NFE AF: 0.198

Gnomad4 OTH AF: 0.288

Alfa AF: 0.213 Hom.: 3882

Bravo AF: 0.304

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.1
DANN	Benign	0.87
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

LitVar

Other links and lift over

dbSNP: rs929533; hg19: chr3-51975577; COSMIC: COSV51756642; COSMIC: COSV51756642;