rs957783084

Variant summary

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

The ENST00000260665.12(LRPPRC):ā€‹c.1390G>Cā€‹(p.Gly464Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000016 in 1,435,142 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 33)
Exomes š‘“: 0.000016 ( 0 hom. )

Consequence

LRPPRC
ENST00000260665.12 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:2

Conservation

PhyloP100: 1.01
Variant links:
Genes affected
LRPPRC (HGNC:15714): (leucine rich pentatricopeptide repeat containing) This gene encodes a leucine-rich protein that has multiple pentatricopeptide repeats (PPR). The precise role of this protein is unknown but studies suggest it may play a role in cytoskeletal organization, vesicular transport, or in transcriptional regulation of both nuclear and mitochondrial genes. The protein localizes primarily to mitochondria and is predicted to have an N-terminal mitochondrial targeting sequence. Mutations in this gene are associated with the French-Canadian type of Leigh syndrome. [provided by RefSeq, Mar 2012]

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=0.07442024).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
LRPPRCNM_133259.4 linkuse as main transcriptc.1390G>C p.Gly464Arg missense_variant 12/38 ENST00000260665.12 NP_573566.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
LRPPRCENST00000260665.12 linkuse as main transcriptc.1390G>C p.Gly464Arg missense_variant 12/381 NM_133259.4 ENSP00000260665 P3

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
0.0000160
AC:
23
AN:
1435142
Hom.:
0
Cov.:
26
AF XY:
0.0000168
AC XY:
12
AN XY:
715648
show subpopulations
Gnomad4 AFR exome
AF:
0.0000304
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:
0.0000184
Gnomad4 OTH exome
AF:
0.0000336
GnomAD4 genome
Cov.:
33
Bravo
AF:
0.00000756

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Congenital lactic acidosis, Saguenay-Lac-Saint-Jean type Uncertain:1
Uncertain significance, no assertion criteria providedclinical testingNatera, Inc.Dec 03, 2020- -
not provided Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingCenter for Pediatric Genomic Medicine, Children's Mercy Hospital and ClinicsSep 28, 2016- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.26
BayesDel_addAF
Benign
-0.21
T
BayesDel_noAF
Benign
-0.54
CADD
Benign
17
DANN
Benign
0.13
DEOGEN2
Benign
0.12
T;T;.
Eigen
Benign
-0.77
Eigen_PC
Benign
-0.74
FATHMM_MKL
Benign
0.51
D
LIST_S2
Benign
0.66
T;T;T
M_CAP
Benign
0.0070
T
MetaRNN
Benign
0.074
T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.8
L;.;.
MutationTaster
Benign
1.0
N;N;N
PrimateAI
Benign
0.26
T
PROVEAN
Benign
-0.93
N;N;N
REVEL
Benign
0.020
Sift
Benign
0.53
T;T;T
Sift4G
Benign
0.52
T;T;T
Polyphen
0.0070
B;.;.
Vest4
0.16
MutPred
0.41
Gain of MoRF binding (P = 0.0286);Gain of MoRF binding (P = 0.0286);Gain of MoRF binding (P = 0.0286);
MVP
0.41
MPC
0.021
ClinPred
0.030
T
GERP RS
2.3
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.037
gMVP
0.42

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs957783084; hg19: chr2-44190825; API