2-43963686-C-G

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_133259.4(LRPPRC):c.1390G>C(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. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G464V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

LRPPRC
NM_133259.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:2

Conservation

PhyloP100: 1.01

Publications

0 publications found

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]

LRPPRC Gene-Disease associations (from GenCC):

congenital lactic acidosis, Saguenay-Lac-Saint-Jean type
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, G2P, Labcorp Genetics (formerly Invitae)
cytochrome-c oxidase deficiency disease
Inheritance: AR Classification: DEFINITIVE Submitted by: Myriad Women’s Health
Leigh syndrome
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen

LRPPRC links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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=0.07442024).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRPPRC	NM_133259.4 link	c.1390G>C	p.Gly464Arg	missense_variant	Exon 12 of 38	ENST00000260665.12	NP_573566.2	P42704E5KNY5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRPPRC	ENST00000260665.12 link	c.1390G>C	p.Gly464Arg	missense_variant	Exon 12 of 38	1	NM_133259.4	ENSP00000260665.7		P42704

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.0000160

AC:

AN:

1435142

Hom.:

Cov.:

AF XY:

0.0000168

AC XY:

AN XY:

715648

show subpopulations

African (AFR)

AF:

0.0000304

AC:

AN:

32866

American (AMR)

AF:

0.00

AC:

AN:

44686

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25954

East Asian (EAS)

AF:

0.00

AC:

AN:

39560

South Asian (SAS)

AF:

0.00

AC:

AN:

85666

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53070

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5726

European-Non Finnish (NFE)

AF:

0.0000184

AC:

AN:

1088152

Other (OTH)

AF:

0.0000336

AC:

AN:

59462

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.408

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

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

Dec 03, 2020

Natera, Inc.

Significance:Uncertain significance

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not provided

Uncertain:1

Sep 28, 2016

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.26

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.54

CADD

Benign

(source)

DANN

Benign

0.13

DEOGEN2

Benign

0.12

T;T;.

Eigen

Benign

-0.77

Eigen_PC

Benign

-0.74

FATHMM_MKL

Benign

0.51

LIST_S2

Benign

0.66

T;T;T

M_CAP

Benign

0.0070

MetaRNN

Benign

0.074

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

L;.;.

PhyloP100

1.0

PrimateAI

Benign

0.26

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

GERP RS

2.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.037

gMVP

0.42

Mutation Taster

=97/3

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over