chr2-43958206-G-A

Variant names:

• chr2-43958206-G-A
• rs10206724
• NM_133259.4:c.1583-755C>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.1583-755C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.715 in 152,094 control chromosomes in the GnomAD database, including 40,479 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 0.71 (40479 hom., cov: 32)
• Consequence: LRPPRC NM_133259.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.64
• Publications: 6 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 = 0.779 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRPPRC	NM_133259.4	c.1583-755C>T		intron_variant	Intron 13 of 37	ENST00000260665.12	NP_573566.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRPPRC	ENST00000260665.12	c.1583-755C>T		intron_variant	Intron 13 of 37	1	NM_133259.4	ENSP00000260665.7

Frequencies

GnomAD3 genomes AF: 0.715 AC: 108651 AN: 151976 Hom.: 40440 Cov.: 32

Gnomad AFR AF: 0.786

Gnomad AMI AF: 0.735

Gnomad AMR AF: 0.607

Gnomad ASJ AF: 0.780

Gnomad EAS AF: 0.0517

Gnomad SAS AF: 0.499

Gnomad FIN AF: 0.765

Gnomad MID AF: 0.816

Gnomad NFE AF: 0.750

Gnomad OTH AF: 0.712

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

GnomAD4 genome AF: 0.715 AC: 108731 AN: 152094 Hom.: 40479 Cov.: 32 AF XY: 0.708 AC XY: 52667 AN XY: 74342

African (AFR) AF: 0.786 AC: 32606 AN: 41484

American (AMR) AF: 0.606 AC: 9255 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.780 AC: 2707 AN: 3472

East Asian (EAS) AF: 0.0516 AC: 267 AN: 5174

South Asian (SAS) AF: 0.500 AC: 2405 AN: 4814

European-Finnish (FIN) AF: 0.765 AC: 8091 AN: 10578

Middle Eastern (MID) AF: 0.820 AC: 241 AN: 294

European-Non Finnish (NFE) AF: 0.750 AC: 51002 AN: 67974

Other (OTH) AF: 0.705 AC: 1487 AN: 2110

Alfa AF: 0.733 Hom.: 172322

Bravo AF: 0.705

Asia WGS AF: 0.319 AC: 1116 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.070
DANN	Benign	0.39
PhyloP100		-1.6
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: rs10206724; hg19: chr2-44185345;