chr17-45962368-A-C
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate
The NM_001377265.1(MAPT):āc.31A>Cā(p.Met11Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000062 in 1,612,210 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Consequence
NM_001377265.1 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MAPT | NM_001377265.1 | c.31A>C | p.Met11Leu | missense_variant | 2/13 | ENST00000262410.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MAPT | ENST00000262410.10 | c.31A>C | p.Met11Leu | missense_variant | 2/13 | 1 | NM_001377265.1 | A2 |
Frequencies
GnomAD3 genomes AF: 0.00000658 AC: 1AN: 152002Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251124Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135724
GnomAD4 exome AF: 0.00000616 AC: 9AN: 1460208Hom.: 0 Cov.: 33 AF XY: 0.00000826 AC XY: 6AN XY: 726394
GnomAD4 genome AF: 0.00000658 AC: 1AN: 152002Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74238
ClinVar
Submissions by phenotype
Frontotemporal dementia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Apr 12, 2022 | This sequence change replaces methionine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 11 of the MAPT protein (p.Met11Leu). This variant is present in population databases (no rsID available, gnomAD 0.004%). This variant has not been reported in the literature in individuals affected with MAPT-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The leucine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at