15-74956499-C-G

Variant names:

• chr15-74956499-C-G
• NM_017793.3:c.85G>C

Variant summary

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

The NM_017793.3(RPP25):​c.85G>C​(p.Ala29Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000719 in 1,390,022 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: RPP25 NM_017793.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.611

Genes affected

RPP25 (HGNC:30361): (ribonuclease P and MRP subunit p25) Enables ribonuclease P RNA binding activity. Contributes to ribonuclease P activity. Involved in tRNA 5'-leader removal. Located in centriolar satellite and nucleoplasm. Part of multimeric ribonuclease P complex and ribonuclease MRP complex. Biomarker of autistic disorder. [provided by Alliance of Genome Resources, Apr 2022]

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=0.05062735).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPP25	NM_017793.3	c.85G>C	p.Ala29Pro	missense_variant	Exon 1 of 1	ENST00000322177.6	NP_060263.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPP25	ENST00000322177.6	c.85G>C	p.Ala29Pro	missense_variant	Exon 1 of 1	6	NM_017793.3	ENSP00000317691.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.19e-7 AC: 1 AN: 1390022 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 686476

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: 0.0000126

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

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	0.083
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	19
DANN	Benign	0.83
DEOGEN2	Benign	0.0056	T
Eigen	Benign	-0.32
Eigen_PC	Benign	-0.13
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.49	T
M_CAP	Benign	0.0055	T
MetaRNN	Benign	0.051	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.97	L
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	2.8	N
REVEL	Benign	0.042
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0050	B
Vest4		0.11
MutPred		0.24		Gain of loop (P = 0.0502);
MVP		0.31
MPC		1.9
ClinPred		0.47	T
GERP RS		4.1
Varity_R		0.42
gMVP		0.47

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: chr15-75248840;