rs373908553
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_133259.4(LRPPRC):āc.1253A>Gā(p.Asn418Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000855 in 1,613,354 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict 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. N418T) has been classified as Uncertain significance.
Frequency
Consequence
NM_133259.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LRPPRC | NM_133259.4 | c.1253A>G | p.Asn418Ser | missense_variant | 10/38 | ENST00000260665.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LRPPRC | ENST00000260665.12 | c.1253A>G | p.Asn418Ser | missense_variant | 10/38 | 1 | NM_133259.4 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.000138 AC: 21AN: 152226Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000876 AC: 22AN: 251158Hom.: 0 AF XY: 0.0000663 AC XY: 9AN XY: 135738
GnomAD4 exome AF: 0.0000794 AC: 116AN: 1461010Hom.: 0 Cov.: 30 AF XY: 0.0000784 AC XY: 57AN XY: 726892
GnomAD4 genome ? AF: 0.000144 AC: 22AN: 152344Hom.: 0 Cov.: 32 AF XY: 0.000161 AC XY: 12AN XY: 74508
ClinVar
Submissions by phenotype
Congenital lactic acidosis, Saguenay-Lac-Saint-Jean type Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Dec 20, 2023 | - - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 14, 2022 | The c.1253A>G (p.N418S) alteration is located in exon 10 (coding exon 10) of the LRPPRC gene. This alteration results from a A to G substitution at nucleotide position 1253, causing the asparagine (N) at amino acid position 418 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 19, 2022 | This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 418 of the LRPPRC protein (p.Asn418Ser). This variant is present in population databases (rs373908553, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with LRPPRC-related conditions. ClinVar contains an entry for this variant (Variation ID: 214585). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt LRPPRC protein function. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 09, 2014 | 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:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at