rs10865196

Variant names:

• chr2-43962491-G-A
• rs10865196
• NM_133259.4:c.1488+1097C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_133259.4(LRPPRC):​c.1488+1097C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.601 in 152,038 control chromosomes in the GnomAD database, including 28,685 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.60 (28685 hom., cov: 33)
• Consequence: LRPPRC NM_133259.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.937
• Publications: 3 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.665 is higher than 0.05.

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.1488+1097C>T		intron	N/A	NP_573566.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRPPRC	ENST00000260665.12	TSL:1 MANE Select	c.1488+1097C>T		intron	N/A	ENSP00000260665.7
	LRPPRC	ENST00000447246.2	TSL:1	c.1488+1097C>T		intron	N/A	ENSP00000403637.2
	LRPPRC	ENST00000409946.6	TSL:1	c.1488+1097C>T		intron	N/A	ENSP00000386234.1

Frequencies

GnomAD3 genomes AF: 0.601 AC: 91292 AN: 151920 Hom.: 28648 Cov.: 33

Gnomad AFR AF: 0.672

Gnomad AMI AF: 0.450

Gnomad AMR AF: 0.533

Gnomad ASJ AF: 0.624

Gnomad EAS AF: 0.0416

Gnomad SAS AF: 0.357

Gnomad FIN AF: 0.663

Gnomad MID AF: 0.694

Gnomad NFE AF: 0.624

Gnomad OTH AF: 0.602

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

GnomAD4 genome AF: 0.601 AC: 91376 AN: 152038 Hom.: 28685 Cov.: 33 AF XY: 0.594 AC XY: 44173 AN XY: 74316

African (AFR) AF: 0.672 AC: 27881 AN: 41492

American (AMR) AF: 0.532 AC: 8117 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.624 AC: 2163 AN: 3464

East Asian (EAS) AF: 0.0415 AC: 215 AN: 5182

South Asian (SAS) AF: 0.359 AC: 1727 AN: 4816

European-Finnish (FIN) AF: 0.663 AC: 7001 AN: 10562

Middle Eastern (MID) AF: 0.699 AC: 204 AN: 292

European-Non Finnish (NFE) AF: 0.624 AC: 42403 AN: 67952

Other (OTH) AF: 0.596 AC: 1256 AN: 2108

Alfa AF: 0.606 Hom.: 112773

Bravo AF: 0.596

Asia WGS AF: 0.253 AC: 886 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.34
DANN	Benign	0.18
PhyloP100		-0.94
Mutation Taster		=100/0	polymorphism (auto)

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: rs10865196; hg19: chr2-44189630;