chr2-68502858-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_173545.3(APLF):c.296G>A(p.Arg99His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000149 in 1,605,386 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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. R99C) has been classified as Likely benign.
Frequency
Consequence
NM_173545.3 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
APLF | NM_173545.3 | c.296G>A | p.Arg99His | missense_variant | 3/10 | ENST00000303795.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
APLF | ENST00000303795.9 | c.296G>A | p.Arg99His | missense_variant | 3/10 | 1 | NM_173545.3 | P1 | |
APLF | ENST00000445692.5 | c.296G>A | p.Arg99His | missense_variant, NMD_transcript_variant | 3/11 | 5 | |||
APLF | ENST00000529851.5 | c.224G>A | p.Arg75His | missense_variant, NMD_transcript_variant | 2/9 | 5 |
Frequencies
GnomAD3 genomes AF: 0.0000395 AC: 6AN: 151988Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000247 AC: 6AN: 242986Hom.: 0 AF XY: 0.0000152 AC XY: 2AN XY: 131838
GnomAD4 exome AF: 0.0000124 AC: 18AN: 1453282Hom.: 0 Cov.: 30 AF XY: 0.00000968 AC XY: 7AN XY: 723116
GnomAD4 genome AF: 0.0000394 AC: 6AN: 152104Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74370
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 12, 2023 | The c.296G>A (p.R99H) alteration is located in exon 3 (coding exon 3) of the APLF gene. This alteration results from a G to A substitution at nucleotide position 296, causing the arginine (R) at amino acid position 99 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