rs1255703512

Variant names:

• chr9-34610836-G-A
• NM_148178.3:c.461C>T

Your query was ambiguous. Multiple possible variants found:

• chr9-34610836-G-A
• chr9-34610836-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_148178.3(RPP25L):​c.461C>T​(p.Ser154Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000036 in 1,388,830 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S154Y) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000036 (0 hom.)
• Consequence: RPP25L NM_148178.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.84

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09994429).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPP25L	NM_148178.3	c.461C>T	p.Ser154Phe	missense_variant	Exon 2 of 2	ENST00000378959.9	NP_680544.1
RPP25L	NM_148179.3	c.461C>T	p.Ser154Phe	missense_variant	Exon 2 of 2		NP_680545.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPP25L	ENST00000378959.9	c.461C>T	p.Ser154Phe	missense_variant	Exon 2 of 2	1	NM_148178.3	ENSP00000368242.4
RPP25L	ENST00000297613.4	c.461C>T	p.Ser154Phe	missense_variant	Exon 2 of 2	2		ENSP00000297613.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000360 AC: 5 AN: 1388830 Hom.: 0 Cov.: 31 AF XY: 0.00000293 AC XY: 2 AN XY: 682216

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000466

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	22
DANN	Benign	0.94
DEOGEN2	Benign	0.057	T;T
Eigen	Benign	-0.35
Eigen_PC	Benign	-0.20
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Benign	0.46	.;T
M_CAP	Benign	0.0038	T
MetaRNN	Benign	0.10	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N;N
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-2.2	N;N
REVEL	Benign	0.046
Sift	Benign	0.042	D;D
Sift4G	Uncertain	0.055	T;T
Polyphen		0.0	B;B
Vest4		0.11
MutPred		0.21		Loss of phosphorylation at S154 (P = 3e-04);Loss of phosphorylation at S154 (P = 3e-04);
MVP		0.043
MPC		0.45
ClinPred		0.32	T
GERP RS		4.4
Varity_R		0.097
gMVP		0.26

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: chr9-34610833;