rs73314997

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The ENST00000262410.10(MAPT):ā€‹c.1178C>Gā€‹(p.Ser393Trp) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,800 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S393L) has been classified as Benign.

Frequency

Genomes: not found (cov: 33)
Exomes š‘“: 6.8e-7 ( 0 hom. )

Consequence

MAPT
ENST00000262410.10 missense

Scores

4
15

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.83
Variant links:
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 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.33540475).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
MAPTNM_001377265.1 linkuse as main transcriptc.1178C>G p.Ser393Trp missense_variant 5/13 ENST00000262410.10 NP_001364194.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
MAPTENST00000262410.10 linkuse as main transcriptc.1178C>G p.Ser393Trp missense_variant 5/131 NM_001377265.1 ENSP00000262410 A2

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461800
Hom.:
0
Cov.:
35
AF XY:
0.00
AC XY:
0
AN XY:
727202
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.13
BayesDel_addAF
Benign
-0.16
T
BayesDel_noAF
Benign
-0.47
CADD
Benign
21
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.51
D;.;.;D
Eigen
Benign
-0.088
Eigen_PC
Benign
-0.25
FATHMM_MKL
Benign
0.25
N
LIST_S2
Benign
0.70
T;T;.;.
M_CAP
Benign
0.034
D
MetaRNN
Benign
0.34
T;T;T;T
MetaSVM
Benign
-1.2
T
MutationAssessor
Benign
1.4
L;L;L;L
MutationTaster
Benign
1.0
D;D;D;D;D;D;D;D;D;D;N;N;N;N
PrimateAI
Benign
0.36
T
PROVEAN
Benign
-1.5
N;N;N;.
REVEL
Benign
0.16
Sift
Uncertain
0.0050
D;D;D;.
Sift4G
Uncertain
0.023
D;D;D;D
Polyphen
0.93
P;P;P;P
Vest4
0.44
MutPred
0.31
Loss of disorder (P = 0.0349);Loss of disorder (P = 0.0349);Loss of disorder (P = 0.0349);Loss of disorder (P = 0.0349);
MVP
0.64
MPC
0.48
ClinPred
0.80
D
GERP RS
4.4
Varity_R
0.10
gMVP
0.18

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs73314997; hg19: chr17-44061123; API