17-46010405-G-C
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001377265.1(MAPT):c.2091+3G>C variant causes a splice donor region, intron change. The variant allele was found at a frequency of 0.000000708 in 1,411,796 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 7.1e-7 ( 0 hom. )
Consequence
MAPT
NM_001377265.1 splice_donor_region, intron
NM_001377265.1 splice_donor_region, intron
Scores
2
Splicing: ADA: 0.9999
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 5.33
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MAPT | NM_001377265.1 | c.2091+3G>C | splice_donor_region_variant, intron_variant | ENST00000262410.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MAPT | ENST00000262410.10 | c.2091+3G>C | splice_donor_region_variant, intron_variant | 1 | NM_001377265.1 | A2 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD3 exomes AF: 0.00000564 AC: 1AN: 177170Hom.: 0 AF XY: 0.0000107 AC XY: 1AN XY: 93658
GnomAD3 exomes
AF:
AC:
1
AN:
177170
Hom.:
AF XY:
AC XY:
1
AN XY:
93658
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 7.08e-7 AC: 1AN: 1411796Hom.: 0 Cov.: 30 AF XY: 0.00000143 AC XY: 1AN XY: 697870
GnomAD4 exome
AF:
AC:
1
AN:
1411796
Hom.:
Cov.:
30
AF XY:
AC XY:
1
AN XY:
697870
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Pathogenic
dbscSNV1_RF
Pathogenic
SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_DL_spliceai
Position offset: -3
Find out detailed SpliceAI scores and Pangolin per-transcript scores at