2-43916201-G-A

Variant names:

• chr2-43916201-G-A
• rs4953035
• NM_133259.4:c.3148+1824C>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.3148+1824C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.627 in 152,136 control chromosomes in the GnomAD database, including 31,823 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 0.63 (31823 hom., cov: 32)
• Consequence: LRPPRC NM_133259.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.237
• Publications: 3 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: G2P, Orphanet, 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
• mitochondrial disease

  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 (EAS) allele frequency at 95% confidence interval = 0.935 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_133259.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRPPRC	NM_133259.4	MANE Select	c.3148+1824C>T		intron	N/A	NP_573566.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRPPRC	ENST00000260665.12	TSL:1 MANE Select	c.3148+1824C>T		intron	N/A	ENSP00000260665.7	P42704
	LRPPRC	ENST00000683125.1		c.3256+1824C>T		intron	N/A	ENSP00000507939.1	A0A804HKI2
	LRPPRC	ENST00000958038.1		c.3148+1824C>T		intron	N/A	ENSP00000628097.1

Frequencies

GnomAD3 genomes AF: 0.627 AC: 95309 AN: 152018 Hom.: 31771 Cov.: 32

Gnomad AFR AF: 0.836

Gnomad AMI AF: 0.627

Gnomad AMR AF: 0.642

Gnomad ASJ AF: 0.521

Gnomad EAS AF: 0.957

Gnomad SAS AF: 0.651

Gnomad FIN AF: 0.479

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.497

Gnomad OTH AF: 0.630

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

GnomAD4 genome AF: 0.627 AC: 95420 AN: 152136 Hom.: 31823 Cov.: 32 AF XY: 0.630 AC XY: 46840 AN XY: 74360

African (AFR) AF: 0.837 AC: 34734 AN: 41518

American (AMR) AF: 0.643 AC: 9831 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.521 AC: 1809 AN: 3472

East Asian (EAS) AF: 0.957 AC: 4970 AN: 5192

South Asian (SAS) AF: 0.649 AC: 3122 AN: 4812

European-Finnish (FIN) AF: 0.479 AC: 5050 AN: 10544

Middle Eastern (MID) AF: 0.602 AC: 177 AN: 294

European-Non Finnish (NFE) AF: 0.497 AC: 33820 AN: 67988

Other (OTH) AF: 0.633 AC: 1336 AN: 2112

Alfa AF: 0.566 Hom.: 3173

Bravo AF: 0.651

Asia WGS AF: 0.774 AC: 2689 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.8
DANN	Benign	0.47
PhyloP100		0.24
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: rs4953035; hg19: chr2-44143340;