chr11-72293407-C-T
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong
The NM_030813.6(CLPB):c.2084G>A(p.Arg695Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000273 in 1,613,998 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict 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. R695W) has been classified as Benign.
Frequency
Consequence
NM_030813.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CLPB | NM_030813.6 | c.2084G>A | p.Arg695Gln | missense_variant | 17/17 | ENST00000294053.9 | |
CLPB | NM_001258392.3 | c.1994G>A | p.Arg665Gln | missense_variant | 16/16 | ENST00000538039.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CLPB | ENST00000294053.9 | c.2084G>A | p.Arg695Gln | missense_variant | 17/17 | 1 | NM_030813.6 | P4 | |
CLPB | ENST00000538039.6 | c.1994G>A | p.Arg665Gln | missense_variant | 16/16 | 2 | NM_001258392.3 | A1 |
Frequencies
GnomAD3 genomes AF: 0.0000460 AC: 7AN: 152130Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000199 AC: 5AN: 251360Hom.: 0 AF XY: 0.0000294 AC XY: 4AN XY: 135864
GnomAD4 exome AF: 0.0000253 AC: 37AN: 1461868Hom.: 0 Cov.: 31 AF XY: 0.0000234 AC XY: 17AN XY: 727232
GnomAD4 genome AF: 0.0000460 AC: 7AN: 152130Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4AN XY: 74304
ClinVar
Submissions by phenotype
3-methylglutaconic aciduria, type VIIB Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 22, 2023 | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 695 of the CLPB protein (p.Arg695Gln). This variant is present in population databases (rs374538248, gnomAD 0.01%). 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: 933673). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The glutamine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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