rs775179184

Variant names:

• chr9-34611283-C-A
• rs775179184
• NM_148178.3:c.14G>T

Your query was ambiguous. Multiple possible variants found:

• chr9-34611283-C-A
• chr9-34611283-C-T

Variant summary

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

The NM_148178.3(RPP25L):​c.14G>T​(p.Arg5Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,606 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R5Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: RPP25L NM_148178.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0680
• Publications: 0 publications found

Genes affected

RPP25L (HGNC:19909): (ribonuclease P/MRP subunit p25 like) This gene encodes a protein that appears to belong to a family of evolutionarily related proteins (DUF78), that may share one or more domains in common. Members of this family are small archaebacterial proteins with no known function. Alternative splicing has been observed at this locus and two variants, both encoding the same protein, have been identified. [provided by RefSeq, Jul 2008]

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=0.12887496).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_148178.3. 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
	RPP25L	NM_148178.3	MANE Select	c.14G>T	p.Arg5Leu	missense	Exon 2 of 2	NP_680544.1	Q8N5L8
	RPP25L	NM_148179.3		c.14G>T	p.Arg5Leu	missense	Exon 2 of 2	NP_680545.1	Q8N5L8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPP25L	ENST00000378959.9	TSL:1 MANE Select	c.14G>T	p.Arg5Leu	missense	Exon 2 of 2	ENSP00000368242.4	Q8N5L8
	RPP25L	ENST00000297613.4	TSL:2	c.14G>T	p.Arg5Leu	missense	Exon 2 of 2	ENSP00000297613.4	Q8N5L8
	RPP25L	ENST00000923013.1		c.14G>T	p.Arg5Leu	missense	Exon 2 of 2	ENSP00000593072.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1460606 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726562

⚠️ 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: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44680

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26082

East Asian (EAS) AF: 0.00 AC: 0 AN: 39686

South Asian (SAS) AF: 0.00 AC: 0 AN: 86230

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52602

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111718

Other (OTH) AF: 0.00 AC: 0 AN: 60370

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0385499), 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	0.23
BayesDel_addAF	Benign	-0.071	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.20	T
Eigen	Benign	-0.13
Eigen_PC	Benign	-0.082
FATHMM_MKL	Benign	0.74	D
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.0072	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	2.0	M
PhyloP100		-0.068
PrimateAI	Uncertain	0.55	T
PROVEAN	Uncertain	-3.5	D
REVEL	Benign	0.12
Sift	Uncertain	0.014	D
Sift4G	Uncertain	0.022	D
Polyphen		0.47	P
Vest4		0.32
MutPred		0.21		Loss of MoRF binding (P = 0.0475)
MVP		0.043
MPC		0.61
ClinPred		0.97	D
GERP RS		3.7
Varity_R		0.37
gMVP		0.57
Mutation Taster		=70/30	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs775179184; hg19: chr9-34611280;