rs776028517
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_ModerateBP6_ModerateBP7
The NM_001377265.1(MAPT):c.1356C>A(p.Arg452=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000186 in 1,613,772 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 Likely benign (★).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000019 ( 0 hom. )
Consequence
MAPT
NM_001377265.1 synonymous
NM_001377265.1 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.958
Genes affected
MAPT (HGNC:6893): (microtubule associated protein tau) This gene encodes the microtubule-associated protein tau (MAPT) whose transcript undergoes complex, regulated alternative splicing, giving rise to several mRNA species. MAPT transcripts are differentially expressed in the nervous system, depending on stage of neuronal maturation and neuron type. MAPT gene mutations have been associated with several neurodegenerative disorders such as Alzheimer's disease, Pick's disease, frontotemporal dementia, cortico-basal degeneration and progressive supranuclear palsy. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -5 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.26).
BP6
?
Variant 17-45987044-C-A is Benign according to our data. Variant chr17-45987044-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 529749.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=0.958 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MAPT | NM_001377265.1 | c.1356C>A | p.Arg452= | synonymous_variant | 6/13 | ENST00000262410.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MAPT | ENST00000262410.10 | c.1356C>A | p.Arg452= | synonymous_variant | 6/13 | 1 | NM_001377265.1 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152150Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251414Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135898
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GnomAD4 exome AF: 0.0000192 AC: 28AN: 1461504Hom.: 0 Cov.: 31 AF XY: 0.0000220 AC XY: 16AN XY: 727060
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GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152268Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74454
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Frontotemporal dementia Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Oct 29, 2023 | - - |
Computational scores
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at