Genetic Variant LRPPRC:p.Lys1049_Gly1050insLysLysLys (chr2-43918025-C-CTTTTTTTTT) – ACMG Classification: Uncertain_significance (4 pts)

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

LRPPRC links:

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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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_133259.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRPPRC	NM_133259.4	MANE Select	c.3147_3148insAAAAAAAAA	p.Lys1049_Gly1050insLysLysLys	conservative_inframe_insertion splice_region	Exon 29 of 38	NP_573566.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
LRPPRC	ENST00000260665.12	TSL:1 MANE Select	c.3147_3148insAAAAAAAAA	p.Lys1049_Gly1050insLysLysLys	conservative_inframe_insertion splice_region	Exon 29 of 38	ENSP00000260665.7
LRPPRC	ENST00000683125.1		c.3255_3256insAAAAAAAAA	p.Lys1085_Gly1086insLysLysLys	conservative_inframe_insertion splice_region	Exon 30 of 39	ENSP00000507939.1
LRPPRC	ENST00000683220.1		c.3177_3178insAAAAAAAAA	p.Lys1059_Gly1060insLysLysLys	conservative_inframe_insertion splice_region	Exon 29 of 38	ENSP00000507151.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

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:

AN:

1444946

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

719382

African (AFR)

AF:

0.00

AC:

AN:

33072

American (AMR)

AF:

0.00

AC:

AN:

44530

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25910

East Asian (EAS)

AF:

0.00

AC:

AN:

39302

South Asian (SAS)

AF:

0.00

AC:

AN:

85902

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53132

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5698

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1097742

Other (OTH)

AF:

0.00

AC:

AN:

59658

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000480

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.3

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over