rs1023018572

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr15-74956535-C-A
• chr15-74956535-C-G
• chr15-74956535-C-T

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>T​(p.Gly17Trp) variant causes a missense change. The variant allele was found at a frequency of 0.000000731 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: 7.3e-7 (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=0.1953972).

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>T	p.Gly17Trp	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>T	p.Gly17Trp	missense	Exon 1 of 1	ENSP00000317691.6	Q9BUL9

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.31e-7 AC: 1 AN: 1368602 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 675454

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

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: 0.0000265 AC: 1 AN: 37692

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1072408

Other (OTH) AF: 0.00 AC: 0 AN: 57012

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.040	T
BayesDel_noAF	Benign	-0.29
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.016	T
Eigen	Benign	-0.20
Eigen_PC	Benign	-0.27
FATHMM_MKL	Benign	0.32	N
LIST_S2	Benign	0.57	T
M_CAP	Benign	0.0081	T
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.97	L
PhyloP100		6.6
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-0.12	N
REVEL	Benign	0.087
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.027	D
Polyphen		0.97	D
Vest4		0.33
MutPred		0.26		Loss of loop (P = 0.0512)
MVP		0.36
MPC		1.8
ClinPred		0.82	D
GERP RS		3.1
PromoterAI		0.00060	Neutral
Varity_R		0.097
gMVP		0.54

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;