chr12-27660886-A-G
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_003622.4(PPFIBP1):āc.847A>Gā(p.Ile283Val) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000992 in 1,613,446 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. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I283M) has been classified as Uncertain significance.
Frequency
Consequence
NM_003622.4 missense, splice_region
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 |
---|---|---|---|---|---|---|---|
PPFIBP1 | NM_003622.4 | c.847A>G | p.Ile283Val | missense_variant, splice_region_variant | 11/30 | ENST00000228425.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PPFIBP1 | ENST00000228425.11 | c.847A>G | p.Ile283Val | missense_variant, splice_region_variant | 11/30 | 1 | NM_003622.4 | P3 |
Frequencies
GnomAD3 genomes AF: 0.0000788 AC: 12AN: 152256Hom.: 0 Cov.: 34
GnomAD3 exomes AF: 0.0000160 AC: 4AN: 250676Hom.: 0 AF XY: 0.00000738 AC XY: 1AN XY: 135496
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1461190Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2AN XY: 726892
GnomAD4 genome AF: 0.0000788 AC: 12AN: 152256Hom.: 0 Cov.: 34 AF XY: 0.000108 AC XY: 8AN XY: 74394
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 14, 2024 | The c.907A>G (p.I303V) alteration is located in exon 11 (coding exon 9) of the PPFIBP1 gene. This alteration results from a A to G substitution at nucleotide position 907, causing the isoleucine (I) at amino acid position 303 to be replaced by a valine (V). 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