Variant rs193920968 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000262410.10(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
ENST00000262410.10 missense

Scores

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 3.04

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]

MAPT links:

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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	Protein	UniProt
MAPT	NM_001377265.1 linkuse as main transcript	c.100G>T	p.Asp34Tyr	missense_variant	2/13	ENST00000262410.10	NP_001364194.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAPT	ENST00000262410.10 linkuse as main transcript	c.100G>T	p.Asp34Tyr	missense_variant	2/13	1	NM_001377265.1	ENSP00000262410	A2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1460610

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726592

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.:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

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: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Pathogenic

0.21

BayesDel_noAF

Uncertain

0.070

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.44

T;.;.;.;.;.;.;.;.;T;.;.

Eigen

Uncertain

0.51

Eigen_PC

Uncertain

0.46

FATHMM_MKL

Uncertain

0.85

LIST_S2

Uncertain

0.96

D;D;D;D;D;D;D;.;.;.;.;.

M_CAP

Uncertain

0.093

MetaRNN

Uncertain

0.61

D;D;D;D;D;D;D;D;D;D;D;D

MetaSVM

Benign

-0.73

MutationAssessor

Benign

1.8

L;L;L;L;L;L;L;L;L;L;L;L

MutationTaster

Benign

0.93

D;D;D;D;D;N;N;N;N;N;N;N;N

PrimateAI

Uncertain

0.58

PROVEAN

Uncertain

-2.7

D;D;D;D;D;D;N;D;D;.;.;.

REVEL

Benign

0.21

Sift

Pathogenic

0.0

D;D;D;D;D;D;D;D;D;.;.;.

Sift4G

Benign

0.071

T;T;T;T;D;D;D;D;T;T;T;T

Polyphen

1.0

D;D;D;.;D;D;D;D;D;D;D;.

Vest4

0.70

MutPred

0.14

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

0.87

MPC

0.70

ClinPred

0.99

GERP RS

4.8

Varity_R

0.44

gMVP

0.37

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

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