chr2-43962199-G-A

Variant names:

• chr2-43962199-G-A
• rs12712901
• NM_133259.4:c.1488+1389C>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+1389C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.411 in 151,958 control chromosomes in the GnomAD database, including 13,567 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 0.41 (13567 hom., cov: 32)
• Consequence: LRPPRC NM_133259.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.529
• 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.482 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRPPRC	NM_133259.4	c.1488+1389C>T		intron_variant	Intron 12 of 37	ENST00000260665.12	NP_573566.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRPPRC	ENST00000260665.12	c.1488+1389C>T		intron_variant	Intron 12 of 37	1	NM_133259.4	ENSP00000260665.7

Frequencies

GnomAD3 genomes AF: 0.411 AC: 62348 AN: 151840 Hom.: 13556 Cov.: 32

Gnomad AFR AF: 0.329

Gnomad AMI AF: 0.330

Gnomad AMR AF: 0.375

Gnomad ASJ AF: 0.471

Gnomad EAS AF: 0.0404

Gnomad SAS AF: 0.322

Gnomad FIN AF: 0.505

Gnomad MID AF: 0.440

Gnomad NFE AF: 0.487

Gnomad OTH AF: 0.398

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

GnomAD4 genome AF: 0.411 AC: 62399 AN: 151958 Hom.: 13567 Cov.: 32 AF XY: 0.407 AC XY: 30191 AN XY: 74250

African (AFR) AF: 0.329 AC: 13637 AN: 41416

American (AMR) AF: 0.374 AC: 5711 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.471 AC: 1633 AN: 3464

East Asian (EAS) AF: 0.0405 AC: 210 AN: 5186

South Asian (SAS) AF: 0.324 AC: 1563 AN: 4818

European-Finnish (FIN) AF: 0.505 AC: 5314 AN: 10526

Middle Eastern (MID) AF: 0.449 AC: 132 AN: 294

European-Non Finnish (NFE) AF: 0.487 AC: 33065 AN: 67958

Other (OTH) AF: 0.395 AC: 834 AN: 2110

Alfa AF: 0.456 Hom.: 3298

Bravo AF: 0.396

Asia WGS AF: 0.217 AC: 756 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.39
DANN	Benign	0.27
PhyloP100		-0.53
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: rs12712901; hg19: chr2-44189338;