Variant 6-5003993-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_006638.4(RPP40):c.10C>G(p.Leu4Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000412 in 1,457,010 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

RPP40
NM_006638.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.580

Variant links:

Genes affected

RPP40 (HGNC:20992): (ribonuclease P/MRP subunit p40) Enables ribonuclease P RNA binding activity. Contributes to ribonuclease P activity. Involved in tRNA 5'-leader removal. Part of multimeric ribonuclease P complex. [provided by Alliance of Genome Resources, Apr 2022]

RPP40 links:

LYRM4-AS1 (HGNC:):

LYRM4-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.2169942).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPP40	NM_006638.4 linkuse as main transcript	c.10C>G	p.Leu4Val	missense_variant	1/8	ENST00000380051.7	NP_006629.2
LYRM4-AS1	NR_126015.1 linkuse as main transcript	n.144+34G>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPP40	ENST00000380051.7 linkuse as main transcript	c.10C>G	p.Leu4Val	missense_variant	1/8	5	NM_006638.4	ENSP00000369391	P1	O75818-1
LYRM4-AS1	ENST00000661080.2 linkuse as main transcript	n.182+34G>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000412

AC:

AN:

1457010

Hom.:

Cov.:

AF XY:

0.00000414

AC XY:

AN XY:

724664

show subpopulations

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:

0.00000540

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 19, 2022

The c.10C>G (p.L4V) alteration is located in exon 1 (coding exon 1) of the RPP40 gene. This alteration results from a C to G substitution at nucleotide position 10, causing the leucine (L) at amino acid position 4 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.099

BayesDel_addAF

Benign

-0.045

BayesDel_noAF

Benign

-0.30

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.0047

T;.;T

Eigen

Benign

-0.36

Eigen_PC

Benign

-0.59

FATHMM_MKL

Benign

0.48

LIST_S2

Benign

0.84

T;T;T

M_CAP

Uncertain

0.094

MetaRNN

Benign

0.22

T;T;T

MetaSVM

Benign

-0.70

MutationAssessor

Benign

1.8

L;L;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Uncertain

0.69

PROVEAN

Benign

-0.55

N;N;.

REVEL

Benign

0.26

Sift

Uncertain

0.024

D;D;.

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

0.99

D;D;.

Vest4

0.22

MutPred

0.21

Loss of disorder (P = 0.1773);Loss of disorder (P = 0.1773);Loss of disorder (P = 0.1773);

MVP

0.57

MPC

0.32

ClinPred

0.58

GERP RS

-2.5

Varity_R

0.21

gMVP

0.44

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over