rs144397565
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 0P and 3B. BP4_ModerateBS1_Supporting
The NM_001377265.1(MAPT):c.233G>A(p.Gly78Asp) variant causes a missense change. The variant allele was found at a frequency of 0.0000266 in 1,613,778 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. G78V) has been classified as Uncertain significance.
Frequency
Consequence
NM_001377265.1 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MAPT | NM_001377265.1 | c.233G>A | p.Gly78Asp | missense_variant | 4/13 | ENST00000262410.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MAPT | ENST00000262410.10 | c.233G>A | p.Gly78Asp | missense_variant | 4/13 | 1 | NM_001377265.1 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.000125 AC: 19AN: 152110Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000438 AC: 11AN: 251408Hom.: 0 AF XY: 0.0000368 AC XY: 5AN XY: 135908
GnomAD4 exome AF: 0.0000144 AC: 21AN: 1461550Hom.: 0 Cov.: 31 AF XY: 0.00000963 AC XY: 7AN XY: 727072
GnomAD4 genome ? AF: 0.000145 AC: 22AN: 152228Hom.: 0 Cov.: 32 AF XY: 0.000121 AC XY: 9AN XY: 74406
ClinVar
Submissions by phenotype
Frontotemporal dementia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | May 09, 2021 | 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: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with MAPT-related conditions. This variant is present in population databases (rs144397565, ExAC 0.06%). This sequence change replaces glycine with aspartic acid at codon 107 of the MAPT protein (p.Gly107Asp). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and aspartic acid. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at