rs63750847
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 4P and 10B. PM1PM5BP4_StrongBP6_ModerateBS2
The NM_000484.4(APP):c.2017G>A(p.Ala673Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000188 in 1,613,936 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 Benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A673V) has been classified as Pathogenic.
Frequency
Consequence
NM_000484.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
APP | NM_000484.4 | c.2017G>A | p.Ala673Thr | missense_variant | 16/18 | ENST00000346798.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
APP | ENST00000346798.8 | c.2017G>A | p.Ala673Thr | missense_variant | 16/18 | 1 | NM_000484.4 |
Frequencies
GnomAD3 genomes ? AF: 0.000283 AC: 43AN: 152186Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000446 AC: 112AN: 251392Hom.: 0 AF XY: 0.000412 AC XY: 56AN XY: 135862
GnomAD4 exome AF: 0.000178 AC: 260AN: 1461750Hom.: 0 Cov.: 30 AF XY: 0.000166 AC XY: 121AN XY: 727186
GnomAD4 genome ? AF: 0.000283 AC: 43AN: 152186Hom.: 0 Cov.: 32 AF XY: 0.000282 AC XY: 21AN XY: 74354
ClinVar
Submissions by phenotype
Alzheimer disease, protection against Benign:1
protective, no assertion criteria provided | literature only | OMIM | Aug 02, 2012 | - - |
Alzheimer disease Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 28, 2024 | - - |
not provided Other:1
not provided, no classification provided | literature only | VIB Department of Molecular Genetics, University of Antwerp | - | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at