NM_000883.4:c.849T>A
Variant summary
Our verdict is Likely pathogenic. The variant received 9 ACMG points: 9P and 0B. PS1PM2PP3PP5_Moderate
The NM_000883.4(IMPDH1):c.849T>A(p.Asn283Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Pathogenic in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N283S) has been classified as Uncertain significance.
Frequency
Consequence
NM_000883.4 missense
Scores
Clinical Significance
Conservation
Publications
- inherited retinal dystrophyInheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
- Leber congenital amaurosis 11Inheritance: AD Classification: DEFINITIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P
- retinitis pigmentosa 10Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
- Leber congenital amaurosisInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- retinitis pigmentosaInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Genome browser will be placed here
ACMG classification
Our verdict: Likely_pathogenic. The variant received 9 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 exome Cov.: 32
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
not provided Pathogenic:1
For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects IMPDH1 function (PMID: 16384941). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 1457411). This variant is also known as Asn198Lys. This missense change has been observed in individual(s) with Leber congenital amaurosis (PMID: 16384941). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces asparagine, which is neutral and polar, with lysine, which is basic and polar, at codon 283 of the IMPDH1 protein (p.Asn283Lys). -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at