15-50908845-G-C
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate
The NM_007347.5(AP4E1):āc.67G>Cā(p.Gly23Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000305 in 1,608,588 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (ā ).
Frequency
Consequence
NM_007347.5 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 | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
AP4E1 | NM_007347.5 | c.67G>C | p.Gly23Arg | missense_variant | 1/21 | ENST00000261842.10 | NP_031373.2 | |
AP4E1 | NM_001252127.2 | c.-182G>C | 5_prime_UTR_variant | 1/21 | NP_001239056.1 | |||
AP4E1 | XM_005254264.5 | c.-76+202G>C | intron_variant | XP_005254321.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
AP4E1 | ENST00000261842.10 | c.67G>C | p.Gly23Arg | missense_variant | 1/21 | 1 | NM_007347.5 | ENSP00000261842 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000328 AC: 5AN: 152232Hom.: 0 Cov.: 34
GnomAD3 exomes AF: 0.00000866 AC: 2AN: 230970Hom.: 0 AF XY: 0.00000787 AC XY: 1AN XY: 127064
GnomAD4 exome AF: 0.0000302 AC: 44AN: 1456356Hom.: 0 Cov.: 31 AF XY: 0.0000221 AC XY: 16AN XY: 724134
GnomAD4 genome AF: 0.0000328 AC: 5AN: 152232Hom.: 0 Cov.: 34 AF XY: 0.0000403 AC XY: 3AN XY: 74370
ClinVar
Submissions by phenotype
Spastic paraplegia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Aug 06, 2020 | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with AP4E1-related conditions. This variant is present in population databases (rs373684336, ExAC 0.003%). This sequence change replaces glycine with arginine at codon 23 of the AP4E1 protein (p.Gly23Arg). The glycine residue is moderately conserved and there is a moderate physicochemical difference between glycine and arginine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at