rs1553411854

Variant names:

• chr2-43977271-C-A
• rs1553411854
• NM_133259.4:c.475G>T

Your query was ambiguous. Multiple possible variants found:

• chr2-43977271-C-A
• chr2-43977271-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_133259.4(LRPPRC):​c.475G>T​(p.Val159Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V159M) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: LRPPRC NM_133259.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.82
• Publications: 0 publications found

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

ACMG classification

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=0.23268428).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRPPRC	NM_133259.4	c.475G>T	p.Val159Leu	missense_variant	Exon 4 of 38	ENST00000260665.12	NP_573566.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRPPRC	ENST00000260665.12	c.475G>T	p.Val159Leu	missense_variant	Exon 4 of 38	1	NM_133259.4	ENSP00000260665.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 27

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.079	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.21	T;T;.;T
Eigen	Benign	-0.16
Eigen_PC	Benign	-0.082
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Uncertain	0.93	D;D;D;D
M_CAP	Benign	0.033	D
MetaRNN	Benign	0.23	T;T;T;T
MetaSVM	Benign	-0.56	T
MutationAssessor	Uncertain	2.6	M;.;.;.
PhyloP100		1.8
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-1.3	N;N;N;N
REVEL	Benign	0.066
Sift	Benign	0.13	T;T;T;T
Sift4G	Uncertain	0.038	D;D;D;D
Polyphen		0.28	B;.;.;B
Vest4		0.32
MutPred		0.41		Loss of methylation at K155 (P = 0.0679);Loss of methylation at K155 (P = 0.0679);Loss of methylation at K155 (P = 0.0679);.;
MVP		0.72
MPC		0.040
ClinPred		0.50	T
GERP RS		3.4
Varity_R		0.086
gMVP		0.24
Mutation Taster		=93/7	polymorphism

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

Other links and lift over

dbSNP: rs1553411854; hg19: chr2-44204410;