11-72293380-C-T
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate
The NM_001258392.3(CLPB):c.2021G>A(p.Cys674Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000434 in 1,613,802 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 (★).
Frequency
Consequence
NM_001258392.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CLPB | NM_030813.6 | c.2111G>A | p.Cys704Tyr | missense_variant | Exon 17 of 17 | ENST00000294053.9 | NP_110440.1 | |
CLPB | NM_001258392.3 | c.2021G>A | p.Cys674Tyr | missense_variant | Exon 16 of 16 | ENST00000538039.6 | NP_001245321.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CLPB | ENST00000294053.9 | c.2111G>A | p.Cys704Tyr | missense_variant | Exon 17 of 17 | 1 | NM_030813.6 | ENSP00000294053.3 | ||
CLPB | ENST00000538039.6 | c.2021G>A | p.Cys674Tyr | missense_variant | Exon 16 of 16 | 2 | NM_001258392.3 | ENSP00000441518.1 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152148Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251148Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135720
GnomAD4 exome AF: 0.00000342 AC: 5AN: 1461654Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2AN XY: 727114
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152148Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74318
ClinVar
Submissions by phenotype
3-methylglutaconic aciduria, type VIIB Uncertain:1
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: "Possibly Damaging"; Align-GVGD: "Class C0"). 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. This variant has not been reported in the literature in individuals affected with CLPB-related conditions. This sequence change replaces cysteine, which is neutral and slightly polar, with tyrosine, which is neutral and polar, at codon 704 of the CLPB protein (p.Cys704Tyr). This variant is present in population databases (rs372096809, gnomAD 0.0009%). -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at