GeneBe

NM_133259.4:c.3147_3148insAAAAAAAAA

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PM4

The NM_133259.4(LRPPRC):​c.3147_3148insAAAAAAAAA​(p.Lys1049_Gly1050insLysLysLys) variant causes a conservative inframe insertion, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 30)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

LRPPRC
NM_133259.4 conservative_inframe_insertion, splice_region

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.33

Publications

5 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

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PM4
Nonframeshift variant in NON repetitive region in NM_133259.4.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
LRPPRCNM_133259.4 linkc.3147_3148insAAAAAAAAA p.Lys1049_Gly1050insLysLysLys conservative_inframe_insertion, splice_region_variant Exon 29 of 38 ENST00000260665.12 NP_573566.2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
LRPPRCENST00000260665.12 linkc.3147_3148insAAAAAAAAA p.Lys1049_Gly1050insLysLysLys conservative_inframe_insertion, splice_region_variant Exon 29 of 38 1 NM_133259.4 ENSP00000260665.7

Frequencies

GnomAD3 genomes
Cov.:
30
GnomAD2 exomes
AF:
0.00
AC:
0
AN:
243620
AF XY:
0.00
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1444946
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
719382
African (AFR)
AF:
0.00
AC:
0
AN:
33072
American (AMR)
AF:
0.00
AC:
0
AN:
44530
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
25910
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39302
South Asian (SAS)
AF:
0.00
AC:
0
AN:
85902
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53132
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5698
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1097742
Other (OTH)
AF:
0.00
AC:
0
AN:
59658
GnomAD4 genome
Cov.:
30
Alfa
AF:
0.0000480
Hom.:
0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
PhyloP100
1.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs769022521; hg19: chr2-44145164; API