15-74956535-C-T

Variant names:

• chr15-74956535-C-T
• rs1023018572
• NM_017793.3:c.49G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_017793.3(RPP25):​c.49G>A​(p.Gly17Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000365 in 1,368,602 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000037 (0 hom.)
• Consequence: RPP25 NM_017793.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.63
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10287389).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017793.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPP25	NM_017793.3	MANE Select	c.49G>A	p.Gly17Arg	missense	Exon 1 of 1	NP_060263.2	Q9BUL9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPP25	ENST00000322177.6	TSL:6 MANE Select	c.49G>A	p.Gly17Arg	missense	Exon 1 of 1	ENSP00000317691.6	Q9BUL9

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000365 AC: 5 AN: 1368602 Hom.: 0 Cov.: 30 AF XY: 0.00000148 AC XY: 1 AN XY: 675454

African (AFR) AF: 0.00 AC: 0 AN: 28646

American (AMR) AF: 0.00 AC: 0 AN: 32406

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23964

East Asian (EAS) AF: 0.00 AC: 0 AN: 33740

South Asian (SAS) AF: 0.00 AC: 0 AN: 77206

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37692

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5528

European-Non Finnish (NFE) AF: 0.00000373 AC: 4 AN: 1072408

Other (OTH) AF: 0.0000175 AC: 1 AN: 57012

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.097	T
BayesDel_noAF	Benign	-0.38
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.016	T
Eigen	Benign	-0.77
Eigen_PC	Benign	-0.68
FATHMM_MKL	Benign	0.26	N
LIST_S2	Benign	0.63	T
M_CAP	Benign	0.0052	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.97	L
PhyloP100		6.6
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	0.060	N
REVEL	Benign	0.045
Sift	Benign	0.073	T
Sift4G	Benign	0.48	T
Polyphen		0.0070	B
Vest4		0.22
MutPred		0.23		Gain of methylation at G17 (P = 0.0266)
MVP		0.25
MPC		1.8
ClinPred		0.92	D
GERP RS		3.1
PromoterAI		-0.053	Neutral
Varity_R		0.052
gMVP		0.49
Mutation Taster		=93/7	polymorphism

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

Other links and lift over

dbSNP: rs1023018572; hg19: chr15-75248876;