NM_000883.4:c.1057G>A
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_000883.4(IMPDH1):c.1057G>A(p.Val353Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000657 in 1,613,166 control chromosomes in the GnomAD database, with no homozygous occurrence. 11/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_000883.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000591 AC: 9AN: 152174Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000480 AC: 12AN: 249824Hom.: 0 AF XY: 0.0000517 AC XY: 7AN XY: 135286
GnomAD4 exome AF: 0.0000664 AC: 97AN: 1460992Hom.: 0 Cov.: 31 AF XY: 0.0000702 AC XY: 51AN XY: 726816
GnomAD4 genome AF: 0.0000591 AC: 9AN: 152174Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3AN XY: 74342
ClinVar
Submissions by phenotype
Retinitis pigmentosa 10 Pathogenic:1
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not provided Uncertain:1
This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 353 of the IMPDH1 protein (p.Val353Ile). This variant is present in population databases (rs121912551, gnomAD 0.008%). This missense change has been observed in individual(s) with retinitis pigmentosa (PMID: 11875050). This variant is also known as V268I. ClinVar contains an entry for this variant (Variation ID: 14835). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. Experimental studies have shown that this missense change affects IMPDH1 function (PMID: 15882147). 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. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at