chr2-43886558-C-G

Variant names:

• chr2-43886558-C-G
• rs998481979
• NM_133259.4:c.*2042G>C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_133259.4(LRPPRC):​c.*2042G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000329 in 152,178 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000033 (0 hom., cov: 32)
• Consequence: LRPPRC NM_133259.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.817

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRPPRC	NM_133259.4	c.*2042G>C		3_prime_UTR_variant	Exon 38 of 38	ENST00000260665.12	NP_573566.2
LRPPRC	XM_006711915.3	c.*2042G>C		3_prime_UTR_variant	Exon 38 of 38		XP_006711978.1
LRPPRC	XM_047442809.1	c.*2042G>C		3_prime_UTR_variant	Exon 38 of 38		XP_047298765.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRPPRC	ENST00000260665	c.*2042G>C		3_prime_UTR_variant	Exon 38 of 38	1	NM_133259.4	ENSP00000260665.7
LRPPRC	ENST00000682612.1	n.*2194G>C		non_coding_transcript_exon_variant	Exon 8 of 8			ENSP00000507966.1
LRPPRC	ENST00000684454.1	n.10091G>C		non_coding_transcript_exon_variant	Exon 7 of 7
LRPPRC	ENST00000682612.1	n.*2194G>C		3_prime_UTR_variant	Exon 8 of 8			ENSP00000507966.1

Frequencies

GnomAD3 genomes AF: 0.0000329 AC: 5 AN: 152178 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 0

GnomAD4 genome AF: 0.0000329 AC: 5 AN: 152178 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74330

Gnomad4 AFR AF: 0.0000483

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000441

Gnomad4 OTH AF: 0.00

Bravo AF: 0.0000302

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.25
DANN	Benign	0.35

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: rs998481979; hg19: chr2-44113697; COSMIC: COSV104591677; COSMIC: COSV104591677;