chr11-72295567-C-T
Variant summary
Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3
The NM_030813.6(CLPB):c.1501G>A(p.Glu501Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000889 in 1,461,840 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. E501D) has been classified as Uncertain significance.
Frequency
Consequence
NM_030813.6 missense
Scores
Clinical Significance
Conservation
Publications
- 3-methylglutaconic aciduria, type VIIBInheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
- neutropenia, severe congenital, 9, autosomal dominantInheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
- Leigh syndromeInheritance: AR Classification: LIMITED Submitted by: ClinGen
Genome browser will be placed here
ACMG classification
Our verdict: Uncertain_significance. The variant received 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CLPB | NM_030813.6 | c.1501G>A | p.Glu501Lys | missense_variant | Exon 13 of 17 | ENST00000294053.9 | NP_110440.1 | |
CLPB | NM_001258392.3 | c.1411G>A | p.Glu471Lys | missense_variant | Exon 12 of 16 | ENST00000538039.6 | NP_001245321.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CLPB | ENST00000294053.9 | c.1501G>A | p.Glu501Lys | missense_variant | Exon 13 of 17 | 1 | NM_030813.6 | ENSP00000294053.3 | ||
CLPB | ENST00000538039.6 | c.1411G>A | p.Glu471Lys | missense_variant | Exon 12 of 16 | 2 | NM_001258392.3 | ENSP00000441518.1 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD2 exomes AF: 0.00000796 AC: 2AN: 251182 AF XY: 0.00 show subpopulations
GnomAD4 exome AF: 0.00000889 AC: 13AN: 1461840Hom.: 0 Cov.: 31 AF XY: 0.00000825 AC XY: 6AN XY: 727220 show subpopulations
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
3-methylglutaconic aciduria, type VIIB Uncertain:1Other:1
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. 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: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 279608). This missense change has been observed in individual(s) with CLPB deficiency who had two additional pathogenic variants in CLPB (PMID: 25597510). This variant is present in population databases (rs748915609, gnomAD 0.002%). This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 501 of the CLPB protein (p.Glu501Lys). -
- -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at