rs193920968
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001377265.1(MAPT):c.100G>T(p.Asp34Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,610 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (no stars).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Consequence
MAPT
NM_001377265.1 missense
NM_001377265.1 missense
Scores
2
11
6
Clinical Significance
Conservation
PhyloP100: 3.04
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 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.100G>T | p.Asp34Tyr | missense_variant | 2/13 | ENST00000262410.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MAPT | ENST00000262410.10 | c.100G>T | p.Asp34Tyr | missense_variant | 2/13 | 1 | NM_001377265.1 | A2 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome AF: 6.85e-7 AC: 1AN: 1460610Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1AN XY: 726592
GnomAD4 exome
AF:
AC:
1
AN:
1460610
Hom.:
Cov.:
33
AF XY:
AC XY:
1
AN XY:
726592
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
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Gnomad4 NFE exome
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Gnomad4 OTH exome
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GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
EpiCase
AF:
EpiControl
AF:
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Malignant tumor of prostate Uncertain:1
Uncertain significance, no assertion criteria provided | literature only | Science for Life laboratory, Karolinska Institutet | - | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Uncertain
T;.;.;.;.;.;.;.;.;T;.;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D;D;D;D;D;.;.;.;.;.
M_CAP
Uncertain
D
MetaRNN
Uncertain
D;D;D;D;D;D;D;D;D;D;D;D
MetaSVM
Benign
T
MutationAssessor
Benign
L;L;L;L;L;L;L;L;L;L;L;L
MutationTaster
Benign
D;D;D;D;D;N;N;N;N;N;N;N;N
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D;D;D;D;D;N;D;D;.;.;.
REVEL
Benign
Sift
Pathogenic
D;D;D;D;D;D;D;D;D;.;.;.
Sift4G
Benign
T;T;T;T;D;D;D;D;T;T;T;T
Polyphen
D;D;D;.;D;D;D;D;D;D;D;.
Vest4
MutPred
Gain of phosphorylation at D34 (P = 0.009);Gain of phosphorylation at D34 (P = 0.009);Gain of phosphorylation at D34 (P = 0.009);Gain of phosphorylation at D34 (P = 0.009);Gain of phosphorylation at D34 (P = 0.009);Gain of phosphorylation at D34 (P = 0.009);Gain of phosphorylation at D34 (P = 0.009);Gain of phosphorylation at D34 (P = 0.009);Gain of phosphorylation at D34 (P = 0.009);Gain of phosphorylation at D34 (P = 0.009);Gain of phosphorylation at D34 (P = 0.009);Gain of phosphorylation at D34 (P = 0.009);
MVP
MPC
0.70
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at