11-72317186-T-A
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP4
The NM_030813.6(CLPB):c.998A>T(p.Glu333Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000496 in 1,611,970 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 Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E333G) has been classified as Likely benign.
Frequency
Consequence
NM_030813.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CLPB | NM_030813.6 | c.998A>T | p.Glu333Val | missense_variant | 8/17 | ENST00000294053.9 | |
CLPB | NM_001258392.3 | c.908A>T | p.Glu303Val | missense_variant | 7/16 | ENST00000538039.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CLPB | ENST00000294053.9 | c.998A>T | p.Glu333Val | missense_variant | 8/17 | 1 | NM_030813.6 | P4 | |
CLPB | ENST00000538039.6 | c.908A>T | p.Glu303Val | missense_variant | 7/16 | 2 | NM_001258392.3 | A1 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152084Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000201 AC: 5AN: 248816Hom.: 0 AF XY: 0.0000149 AC XY: 2AN XY: 134516
GnomAD4 exome AF: 0.00000342 AC: 5AN: 1459886Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1AN XY: 726228
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152084Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74294
ClinVar
Submissions by phenotype
3-methylglutaconic aciduria, type VIIB Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Mar 24, 2023 | 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. 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 disruptive. ClinVar contains an entry for this variant (Variation ID: 1405738). This variant has not been reported in the literature in individuals affected with CLPB-related conditions. This variant is present in population databases (rs144712077, gnomAD 0.03%). This sequence change replaces glutamic acid, which is acidic and polar, with valine, which is neutral and non-polar, at codon 333 of the CLPB protein (p.Glu333Val). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at