rs863225445

chr2-43934197-ATCT-A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM4_Supporting PP5_Moderate

The NM_133259.4(LRPPRC):c.2726_2728del(p.Lys909del) variant causes a inframe deletion change. Variant has been reported in ClinVar as Pathogenic (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: LRPPRC NM_133259.4 inframe_deletion
• Clinical Significance: Pathogenic criteria provided, single submitter P:2
• Conservation: PhyloP100: 5.90

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_133259.4. Strenght limited to Supporting due to length of the change: 1aa.
• PP5: Variant 2-43934197-ATCT-A is Pathogenic according to our data. Variant chr2-43934197-ATCT-A is described in ClinVar as [Pathogenic]. Clinvar id is 218167.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRPPRC	NM_133259.4	c.2726_2728del	p.Lys909del	inframe_deletion	25/38	ENST00000260665.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRPPRC	ENST00000260665.12	c.2726_2728del	p.Lys909del	inframe_deletion	25/38	1	NM_133259.4	P3

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:2

Revision: criteria provided, single submitter

Submissions by phenotype

Congenital lactic acidosis, Saguenay-Lac-Saint-Jean type Pathogenic:2

Pathogenic, criteria provided, single submitter	clinical testing	Institute of Human Genetics Munich, Klinikum Rechts Der Isar, TU München	Oct 25, 2017	- -
Pathogenic, no assertion criteria provided	literature only	OMIM	Dec 01, 2015	- -

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs863225445; hg19: chr2-44161336;