1-218307594-G-A

Position:

• chr1-218307594-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_016052.4(RRP15):​c.667G>A​(p.Glu223Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000219 in 1,461,656 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000022 (0 hom.)
• Consequence: RRP15 NM_016052.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.952

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06416559).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RRP15	NM_016052.4	c.667G>A	p.Glu223Lys	missense_variant	4/5	ENST00000366932.4
RRP15	XM_047421797.1	c.676G>A	p.Glu226Lys	missense_variant	4/5
RRP15	XM_011509597.4	c.667G>A	p.Glu223Lys	missense_variant	4/5
RRP15	XM_047421798.1	c.676G>A	p.Glu226Lys	missense_variant	4/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RRP15	ENST00000366932.4	c.667G>A	p.Glu223Lys	missense_variant	4/5	1	NM_016052.4	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000119 AC: 3 AN: 251078 Hom.: 0 AF XY: 0.00000737 AC XY: 1 AN XY: 135710

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000290

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000219 AC: 32 AN: 1461656 Hom.: 0 Cov.: 31 AF XY: 0.0000220 AC XY: 16 AN XY: 727124

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000224

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: 0.0000279

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	17
DANN	Benign	0.96
DEOGEN2	Benign	0.0026	T
Eigen	Benign	-0.59
Eigen_PC	Benign	-0.52
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.63	T
M_CAP	Benign	0.0061	T
MetaRNN	Benign	0.064	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.7	M
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.34	N
REVEL	Benign	0.035
Sift	Benign	0.53	T
Sift4G	Benign	0.78	T
Polyphen		0.040	B
Vest4		0.20
MutPred		0.29		Gain of MoRF binding (P = 0.0064);
MVP		0.18
MPC		0.064
ClinPred		0.11	T
GERP RS		3.8
Varity_R		0.037
gMVP		0.12

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: rs1558206499; hg19: chr1-218480936;