11-72293432-T-A
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate
The NM_001258392.3(CLPB):c.1969A>T(p.Ser657Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000223 in 1,614,076 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.2059A>T | p.Ser687Cys | missense_variant | Exon 17 of 17 | ENST00000294053.9 | NP_110440.1 | |
CLPB | NM_001258392.3 | c.1969A>T | p.Ser657Cys | 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.2059A>T | p.Ser687Cys | missense_variant | Exon 17 of 17 | 1 | NM_030813.6 | ENSP00000294053.3 | ||
CLPB | ENST00000538039.6 | c.1969A>T | p.Ser657Cys | missense_variant | Exon 16 of 16 | 2 | NM_001258392.3 | ENSP00000441518.1 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152192Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251412Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135898
GnomAD4 exome AF: 0.0000239 AC: 35AN: 1461884Hom.: 0 Cov.: 31 AF XY: 0.0000124 AC XY: 9AN XY: 727244
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152192Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74342
ClinVar
Submissions by phenotype
3-methylglutaconic aciduria, type VIIB Uncertain:1
This sequence change replaces serine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 687 of the CLPB protein (p.Ser687Cys). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with CLPB-related conditions. ClinVar contains an entry for this variant (Variation ID: 1006915). 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. 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 provided Uncertain:1
CLPB: PM2, BP4 -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at