rs145541719
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS1
The NM_007347.5(AP4E1):āc.791A>Gā(p.Asn264Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00027 in 1,614,146 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N264D) has been classified as Uncertain significance.
Frequency
Consequence
NM_007347.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AP4E1 | NM_007347.5 | c.791A>G | p.Asn264Ser | missense_variant | 7/21 | ENST00000261842.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AP4E1 | ENST00000261842.10 | c.791A>G | p.Asn264Ser | missense_variant | 7/21 | 1 | NM_007347.5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000315 AC: 48AN: 152186Hom.: 1 Cov.: 30
GnomAD3 exomes AF: 0.000613 AC: 154AN: 251316Hom.: 0 AF XY: 0.000611 AC XY: 83AN XY: 135816
GnomAD4 exome AF: 0.000265 AC: 388AN: 1461842Hom.: 1 Cov.: 31 AF XY: 0.000294 AC XY: 214AN XY: 727220
GnomAD4 genome AF: 0.000315 AC: 48AN: 152304Hom.: 1 Cov.: 30 AF XY: 0.000389 AC XY: 29AN XY: 74462
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Dec 18, 2016 | - - |
Spastic paraplegia Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Nov 21, 2023 | - - |
AP4E1-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Dec 18, 2019 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at