rs1052553
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_001377265.1(MAPT):āc.1857A>Gā(p.Ala619=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.191 in 1,600,658 control chromosomes in the GnomAD database, including 32,929 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ā ).
Frequency
Genomes: š 0.15 ( 2153 hom., cov: 31)
Exomes š: 0.20 ( 30776 hom. )
Consequence
MAPT
NM_001377265.1 synonymous
NM_001377265.1 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -3.43
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 Benign. Variant got -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.85).
BP6
?
Variant 17-45996523-A-G is Benign according to our data. Variant chr17-45996523-A-G is described in ClinVar as [Benign]. Clinvar id is 98207.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-45996523-A-G is described in Lovd as [Benign].
BP7
?
Synonymous conserved (PhyloP=-3.43 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.215 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MAPT | NM_001377265.1 | c.1857A>G | p.Ala619= | synonymous_variant | 9/13 | ENST00000262410.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MAPT | ENST00000262410.10 | c.1857A>G | p.Ala619= | synonymous_variant | 9/13 | 1 | NM_001377265.1 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.147 AC: 22120AN: 150680Hom.: 2155 Cov.: 31
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GnomAD3 exomes AF: 0.145 AC: 35916AN: 248312Hom.: 3452 AF XY: 0.148 AC XY: 19960AN XY: 134616
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GnomAD4 exome AF: 0.196 AC: 283520AN: 1449850Hom.: 30776 Cov.: 53 AF XY: 0.193 AC XY: 139237AN XY: 721366
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GnomAD4 genome ? AF: 0.147 AC: 22110AN: 150808Hom.: 2153 Cov.: 31 AF XY: 0.138 AC XY: 10132AN XY: 73648
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ClinVar
Significance: Benign
Submissions summary: Benign:9Other:1
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:6
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, Amsterdam University Medical Center | - | - - |
Benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Feb 25, 2011 | - - |
not provided Benign:1Other:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Aug 11, 2018 | - - |
not provided, no classification provided | literature only | VIB Department of Molecular Genetics, University of Antwerp | - | - - |
MAPT-Related Spectrum Disorders Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Frontotemporal dementia Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at