3-49284047-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_003363.4(USP4):c.2480G>A(p.Arg827His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,892 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 13/21 in silico tools predict a damaging 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. R827C) has been classified as Uncertain significance.
Frequency
Consequence
NM_003363.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
USP4 | ENST00000265560.9 | c.2480G>A | p.Arg827His | missense_variant | Exon 19 of 22 | 1 | NM_003363.4 | ENSP00000265560.4 | ||
USP4 | ENST00000351842.8 | c.2339G>A | p.Arg780His | missense_variant | Exon 18 of 21 | 1 | ENSP00000341028.4 | |||
USP4 | ENST00000431357.1 | c.1694G>A | p.Arg565His | missense_variant | Exon 13 of 15 | 5 | ENSP00000399079.1 | |||
USP4 | ENST00000485450.5 | n.2994G>A | non_coding_transcript_exon_variant | Exon 13 of 16 | 2 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251492Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135920
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461892Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2AN XY: 727248
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
not specified Uncertain:1
The c.2480G>A (p.R827H) alteration is located in exon 19 (coding exon 19) of the USP4 gene. This alteration results from a G to A substitution at nucleotide position 2480, causing the arginine (R) at amino acid position 827 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at