chr2-43918330-G-A
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBS1_Supporting
The NM_133259.4(LRPPRC):c.2965C>T(p.Arg989Cys) variant causes a missense change. The variant allele was found at a frequency of 0.000149 in 1,608,972 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R989H) has been classified as Uncertain significance.
Frequency
Consequence
NM_133259.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LRPPRC | NM_133259.4 | c.2965C>T | p.Arg989Cys | missense_variant | 28/38 | ENST00000260665.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LRPPRC | ENST00000260665.12 | c.2965C>T | p.Arg989Cys | missense_variant | 28/38 | 1 | NM_133259.4 | P3 |
Frequencies
GnomAD3 genomes AF: 0.000171 AC: 26AN: 152006Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.000474 AC: 119AN: 251040Hom.: 0 AF XY: 0.000457 AC XY: 62AN XY: 135702
GnomAD4 exome AF: 0.000147 AC: 214AN: 1456848Hom.: 0 Cov.: 30 AF XY: 0.000172 AC XY: 125AN XY: 725158
GnomAD4 genome AF: 0.000164 AC: 25AN: 152124Hom.: 0 Cov.: 31 AF XY: 0.000229 AC XY: 17AN XY: 74368
ClinVar
Submissions by phenotype
Congenital lactic acidosis, Saguenay-Lac-Saint-Jean type Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Oct 31, 2018 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
not provided Uncertain:1Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 25, 2024 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Apr 29, 2021 | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 31130284, 30271085, 32962729) - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at