10-15103764-A-T
Position:
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_183005.5(RPP38):c.450A>T(p.Leu150Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000322 in 1,613,866 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000034 ( 0 hom. )
Consequence
RPP38
NM_183005.5 missense
NM_183005.5 missense
Scores
3
8
7
Clinical Significance
Conservation
PhyloP100: 0.129
Genes affected
RPP38 (HGNC:30329): (ribonuclease P/MRP subunit p38) Enables ribonuclease P RNA binding activity. Contributes to ribonuclease P activity. Involved in tRNA 5'-leader removal. Located in fibrillar center. Part of multimeric ribonuclease P complex. [provided by Alliance of Genome Resources, Apr 2022]
NMT2 (HGNC:7858): (N-myristoyltransferase 2) This gene encodes one of two N-myristoyltransferase proteins. N-terminal myristoylation is a lipid modification that is involved in regulating the function and localization of signaling proteins. The encoded protein catalyzes the addition of a myristoyl group to the N-terminal glycine residue of many signaling proteins, including the human immunodeficiency virus type 1 (HIV-1) proteins, Gag and Nef. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2015]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -4 ACMG points.
BS2
High AC in GnomAdExome4 at 50 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RPP38 | NM_183005.5 | c.450A>T | p.Leu150Phe | missense_variant | 3/3 | ENST00000378197.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RPP38 | ENST00000378197.5 | c.450A>T | p.Leu150Phe | missense_variant | 3/3 | 1 | NM_183005.5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152144Hom.: 0 Cov.: 32
GnomAD3 genomes
AF:
AC:
2
AN:
152144
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.0000160 AC: 4AN: 250286Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135432
GnomAD3 exomes
AF:
AC:
4
AN:
250286
Hom.:
AF XY:
AC XY:
2
AN XY:
135432
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0000342 AC: 50AN: 1461722Hom.: 0 Cov.: 34 AF XY: 0.0000371 AC XY: 27AN XY: 727144
GnomAD4 exome
AF:
AC:
50
AN:
1461722
Hom.:
Cov.:
34
AF XY:
AC XY:
27
AN XY:
727144
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152144Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74322
GnomAD4 genome
AF:
AC:
2
AN:
152144
Hom.:
Cov.:
32
AF XY:
AC XY:
1
AN XY:
74322
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
ExAC
AF:
AC:
2
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 | Aug 13, 2021 | The c.450A>T (p.L150F) alteration is located in exon 3 (coding exon 1) of the RPP38 gene. This alteration results from a A to T substitution at nucleotide position 450, causing the leucine (L) at amino acid position 150 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T;T;T;T;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
D
M_CAP
Benign
D
MetaRNN
Uncertain
D;D;D;D;D
MetaSVM
Uncertain
T
MutationAssessor
Pathogenic
H;H;H;H;.
MutationTaster
Benign
D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;.;D;D;D
REVEL
Uncertain
Sift
Uncertain
D;.;D;D;D
Sift4G
Pathogenic
D;D;D;D;D
Polyphen
D;D;D;D;.
Vest4
MutPred
Gain of sheet (P = 0.1208);Gain of sheet (P = 0.1208);Gain of sheet (P = 0.1208);Gain of sheet (P = 0.1208);Gain of sheet (P = 0.1208);
MVP
MPC
0.48
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at