rs13387221

Variant names:

• chr2-43908175-G-A
• rs13387221
• NM_133259.4:c.3276-2395C>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.3276-2395C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.214 in 152,046 control chromosomes in the GnomAD database, including 3,770 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 0.21 (3770 hom., cov: 32)
• Consequence: LRPPRC NM_133259.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.246
• Publications: 16 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.441 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRPPRC	NM_133259.4	c.3276-2395C>T		intron_variant	Intron 30 of 37	ENST00000260665.12	NP_573566.2
LRPPRC	XM_006711915.3	c.3198-2395C>T		intron_variant	Intron 30 of 37		XP_006711978.1
LRPPRC	XM_047442809.1	c.3150-2395C>T		intron_variant	Intron 30 of 37		XP_047298765.1
LRPPRC	XR_007068563.1	n.3318-2395C>T		intron_variant	Intron 30 of 37

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRPPRC	ENST00000260665.12	c.3276-2395C>T		intron_variant	Intron 30 of 37	1	NM_133259.4	ENSP00000260665.7

Frequencies

GnomAD3 genomes AF: 0.214 AC: 32560 AN: 151928 Hom.: 3774 Cov.: 32

Gnomad AFR AF: 0.239

Gnomad AMI AF: 0.158

Gnomad AMR AF: 0.239

Gnomad ASJ AF: 0.135

Gnomad EAS AF: 0.457

Gnomad SAS AF: 0.309

Gnomad FIN AF: 0.183

Gnomad MID AF: 0.150

Gnomad NFE AF: 0.179

Gnomad OTH AF: 0.210

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

GnomAD4 genome AF: 0.214 AC: 32566 AN: 152046 Hom.: 3770 Cov.: 32 AF XY: 0.217 AC XY: 16154 AN XY: 74306

African (AFR) AF: 0.239 AC: 9915 AN: 41486

American (AMR) AF: 0.240 AC: 3664 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.135 AC: 467 AN: 3468

East Asian (EAS) AF: 0.456 AC: 2348 AN: 5150

South Asian (SAS) AF: 0.308 AC: 1482 AN: 4818

European-Finnish (FIN) AF: 0.183 AC: 1929 AN: 10552

Middle Eastern (MID) AF: 0.151 AC: 44 AN: 292

European-Non Finnish (NFE) AF: 0.178 AC: 12128 AN: 67964

Other (OTH) AF: 0.211 AC: 445 AN: 2110

Alfa AF: 0.193 Hom.: 10152

Bravo AF: 0.219

Asia WGS AF: 0.356 AC: 1234 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	6.6
DANN	Benign	0.69
PhyloP100		0.25
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs13387221; hg19: chr2-44135314;