1-154946412-C-A
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_020524.4(PBXIP1):c.1262G>T(p.Arg421Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000112 in 1,611,030 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. R421C) has been classified as Uncertain significance.
Frequency
Consequence
NM_020524.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PBXIP1 | NM_020524.4 | c.1262G>T | p.Arg421Leu | missense_variant | 10/11 | ENST00000368463.8 | |
PBXIP1 | NM_001317734.2 | c.1175G>T | p.Arg392Leu | missense_variant | 9/10 | ||
PBXIP1 | NM_001317735.2 | c.797G>T | p.Arg266Leu | missense_variant | 7/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PBXIP1 | ENST00000368463.8 | c.1262G>T | p.Arg421Leu | missense_variant | 10/11 | 1 | NM_020524.4 | P2 | |
PBXIP1 | ENST00000368465.5 | c.1175G>T | p.Arg392Leu | missense_variant | 9/10 | 2 | A2 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152234Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000201 AC: 5AN: 248682Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 134746
GnomAD4 exome AF: 0.0000110 AC: 16AN: 1458796Hom.: 0 Cov.: 35 AF XY: 0.0000110 AC XY: 8AN XY: 725828
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152234Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74368
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 24, 2022 | The c.1262G>T (p.R421L) alteration is located in exon 10 (coding exon 9) of the PBXIP1 gene. This alteration results from a G to T substitution at nucleotide position 1262, causing the arginine (R) at amino acid position 421 to be replaced by a leucine (L). 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