chr1-151399655-G-A
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_002796.3(PSMB4):c.68G>A(p.Arg23His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000211 in 1,614,138 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. R23C) has been classified as Uncertain significance.
Frequency
Consequence
NM_002796.3 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/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PSMB4 | NM_002796.3 | c.68G>A | p.Arg23His | missense_variant | 1/7 | ENST00000290541.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PSMB4 | ENST00000290541.7 | c.68G>A | p.Arg23His | missense_variant | 1/7 | 1 | NM_002796.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152152Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251186Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135878
GnomAD4 exome AF: 0.0000150 AC: 22AN: 1461868Hom.: 0 Cov.: 30 AF XY: 0.0000151 AC XY: 11AN XY: 727230
GnomAD4 genome ? AF: 0.0000788 AC: 12AN: 152270Hom.: 0 Cov.: 31 AF XY: 0.000121 AC XY: 9AN XY: 74448
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jun 14, 2023 | ClinVar contains an entry for this variant (Variation ID: 1380676). This variant has not been reported in the literature in individuals affected with PSMB4-related conditions. This variant is present in population databases (rs115066321, gnomAD 0.007%). This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 23 of the PSMB4 protein (p.Arg23His). 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 histidine 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