chr2-68502857-C-T
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate
The NM_173545.3(APLF):c.295C>T(p.Arg99Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000436 in 1,606,260 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 Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R99H) has been classified as Uncertain significance.
Frequency
Consequence
NM_173545.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
APLF | NM_173545.3 | c.295C>T | p.Arg99Cys | missense_variant | 3/10 | ENST00000303795.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
APLF | ENST00000303795.9 | c.295C>T | p.Arg99Cys | missense_variant | 3/10 | 1 | NM_173545.3 | P1 | |
APLF | ENST00000445692.5 | c.295C>T | p.Arg99Cys | missense_variant, NMD_transcript_variant | 3/11 | 5 | |||
APLF | ENST00000529851.5 | c.223C>T | p.Arg75Cys | missense_variant, NMD_transcript_variant | 2/9 | 5 |
Frequencies
GnomAD3 genomes AF: 0.0000460 AC: 7AN: 152020Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000103 AC: 25AN: 243532Hom.: 0 AF XY: 0.000121 AC XY: 16AN XY: 132050
GnomAD4 exome AF: 0.0000433 AC: 63AN: 1454124Hom.: 0 Cov.: 30 AF XY: 0.0000511 AC XY: 37AN XY: 723518
GnomAD4 genome AF: 0.0000460 AC: 7AN: 152136Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74386
ClinVar
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 05, 2023 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at