rs13387221

chr2-43908175-G-A

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
LRPPRC	NM_133259.4	c.3276-2395C>T		intron_variant		ENST00000260665.12
LRPPRC	XM_006711915.3	c.3198-2395C>T		intron_variant
LRPPRC	XM_047442809.1	c.3150-2395C>T		intron_variant
LRPPRC	XR_007068563.1	n.3318-2395C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRPPRC	ENST00000260665.12	c.3276-2395C>T		intron_variant		1	NM_133259.4	P3

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

Gnomad4 AFR AF: 0.239

Gnomad4 AMR AF: 0.240

Gnomad4 ASJ AF: 0.135

Gnomad4 EAS AF: 0.456

Gnomad4 SAS AF: 0.308

Gnomad4 FIN AF: 0.183

Gnomad4 NFE AF: 0.178

Gnomad4 OTH AF: 0.211

Alfa AF: 0.186 Hom.: 5708

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
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Publications

LitVar

Other links and lift over

dbSNP: rs13387221; hg19: chr2-44135314;