2-43901773-C-T

Position:

• chr2-43901773-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_133259.4(LRPPRC):​c.3365-249G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.482 in 470,732 control chromosomes in the GnomAD database, including 59,803 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.51 (21602 hom., cov: 32)
  • Exomes 𝑓: 0.47 (38201 hom.)
• Consequence: LRPPRC NM_133259.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.597

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 2-43901773-C-T is Benign according to our data. Variant chr2-43901773-C-T is described in ClinVar as [Benign]. Clinvar id is 671284.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.93 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRPPRC	NM_133259.4	c.3365-249G>A		intron_variant		ENST00000260665.12
LRPPRC	XM_006711915.3	c.3287-249G>A		intron_variant
LRPPRC	XM_047442809.1	c.3239-249G>A		intron_variant
LRPPRC	XR_007068563.1	n.3407-249G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRPPRC	ENST00000260665.12	c.3365-249G>A		intron_variant		1	NM_133259.4	P3

Frequencies

GnomAD3 genomes AF: 0.513 AC: 77789 AN: 151758 Hom.: 21551 Cov.: 32

Gnomad AFR AF: 0.670

Gnomad AMI AF: 0.479

Gnomad AMR AF: 0.577

Gnomad ASJ AF: 0.384

Gnomad EAS AF: 0.953

Gnomad SAS AF: 0.517

Gnomad FIN AF: 0.400

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.393

Gnomad OTH AF: 0.527

GnomAD4 exome AF: 0.467 AC: 149041 AN: 318858 Hom.: 38201 Cov.: 0 AF XY: 0.466 AC XY: 78931 AN XY: 169240

Gnomad4 AFR exome AF: 0.688

Gnomad4 AMR exome AF: 0.616

Gnomad4 ASJ exome AF: 0.407

Gnomad4 EAS exome AF: 0.939

Gnomad4 SAS exome AF: 0.487

Gnomad4 FIN exome AF: 0.422

Gnomad4 NFE exome AF: 0.399

Gnomad4 OTH exome AF: 0.464

GnomAD4 genome AF: 0.513 AC: 77902 AN: 151874 Hom.: 21602 Cov.: 32 AF XY: 0.517 AC XY: 38355 AN XY: 74206

Gnomad4 AFR AF: 0.670

Gnomad4 AMR AF: 0.578

Gnomad4 ASJ AF: 0.384

Gnomad4 EAS AF: 0.953

Gnomad4 SAS AF: 0.517

Gnomad4 FIN AF: 0.400

Gnomad4 NFE AF: 0.393

Gnomad4 OTH AF: 0.531

Alfa AF: 0.421 Hom.: 7554

Bravo AF: 0.536

Asia WGS AF: 0.709 AC: 2462 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 14, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.39
DANN	Benign	0.82

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: rs4953032; hg19: chr2-44128912;