NM_001377265.1:c.1564T>C

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001377265.1(MAPT):c.1564T>C(p.Ser522Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.189 in 1,613,906 control chromosomes in the GnomAD database, including 32,818 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.14 ( 2147 hom., cov: 32)

Exomes 𝑓: 0.19 ( 30671 hom. )

Consequence

MAPT
NM_001377265.1 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8O:1

Conservation

PhyloP100: 1.05

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0015476942).

BP6

Variant 17-45990034-T-C is Benign according to our data. Variant chr17-45990034-T-C is described in ClinVar as [Benign]. Clinvar id is 98203.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-45990034-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.214 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAPT	NM_001377265.1 link	c.1564T>C	p.Ser522Pro	missense_variant	Exon 7 of 13	ENST00000262410.10	NP_001364194.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAPT	ENST00000262410.10 link	c.1564T>C	p.Ser522Pro	missense_variant	Exon 7 of 13	1	NM_001377265.1	ENSP00000262410.6		A0A7I2PJZ2

Frequencies

GnomAD3 genomes

AF:

0.145

AC:

22074

AN:

152084

Hom.:

2149

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0492

Gnomad AMI

AF:

0.276

Gnomad AMR

AF:

0.176

Gnomad ASJ

AF:

0.240

Gnomad EAS

AF:

0.00154

Gnomad SAS

AF:

0.0741

Gnomad FIN

AF:

0.0652

Gnomad MID

AF:

0.218

Gnomad NFE

AF:

0.217

Gnomad OTH

AF:

0.186

GnomAD3 exomes

AF:

0.146

AC:

36637

AN:

251458

Hom.:

3558

AF XY:

0.149

AC XY:

20262

AN XY:

135898

show subpopulations

Gnomad AFR exome

AF:

0.0474

Gnomad AMR exome

AF:

0.119

Gnomad ASJ exome

AF:

0.254

Gnomad EAS exome

AF:

0.000652

Gnomad SAS exome

AF:

0.0761

Gnomad FIN exome

AF:

0.0681

Gnomad NFE exome

AF:

0.214

Gnomad OTH exome

AF:

0.175

GnomAD4 exome

AF:

0.194

AC:

282964

AN:

1461704

Hom.:

30671

Cov.:

AF XY:

0.191

AC XY:

138977

AN XY:

727164

show subpopulations

Gnomad4 AFR exome

AF:

0.0431

Gnomad4 AMR exome

AF:

0.126

Gnomad4 ASJ exome

AF:

0.256

Gnomad4 EAS exome

AF:

0.000882

Gnomad4 SAS exome

AF:

0.0796

Gnomad4 FIN exome

AF:

0.0724

Gnomad4 NFE exome

AF:

0.222

Gnomad4 OTH exome

AF:

0.177

GnomAD4 genome

AF:

0.145

AC:

22064

AN:

152202

Hom.:

2147

Cov.:

AF XY:

0.136

AC XY:

10119

AN XY:

74422

show subpopulations

Gnomad4 AFR

AF:

0.0491

Gnomad4 AMR

AF:

0.175

Gnomad4 ASJ

AF:

0.240

Gnomad4 EAS

AF:

0.00154

Gnomad4 SAS

AF:

0.0742

Gnomad4 FIN

AF:

0.0652

Gnomad4 NFE

AF:

0.217

Gnomad4 OTH

AF:

0.183

Alfa

AF:

0.203

Hom.:

5700

Bravo

AF:

0.150

TwinsUK

AF:

0.234

AC:

866

ALSPAC

AF:

0.242

AC:

932

ESP6500AA

AF:

0.0511

AC:

225

ESP6500EA

AF:

0.223

AC:

1917

ExAC

AF:

0.145

AC:

17587

Asia WGS

AF:

0.0320

AC:

112

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:8Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Genome Diagnostics Laboratory, Amsterdam University Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided

Benign:2Other:1

VIB Department of Molecular Genetics, University of Antwerp

Significance: not provided

Review Status: no classification provided

Collection Method: literature only

- -

Aug 11, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 30389748, 23222517) -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Frontotemporal dementia

Benign:2

Jan 14, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

May 28, 2019

Mendelics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.043

BayesDel_addAF

Benign

-0.74

BayesDel_noAF

Benign

-0.69

CADD

Benign

DANN

Benign

0.36

DEOGEN2

Benign

0.28

T;.;.;T

Eigen

Benign

-0.85

Eigen_PC

Benign

-0.55

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.21

T;T;.;.

MetaRNN

Benign

0.0015

T;T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

-1.6

N;N;N;N

PrimateAI

Benign

0.41

PROVEAN

Benign

0.78

N;N;N;.

REVEL

Benign

0.064

Sift

Benign

1.0

T;T;T;.

Sift4G

Benign

0.60

T;T;T;T

Polyphen

0.0

B;B;B;B

Vest4

0.076

MPC

0.19

ClinPred

0.0014

GERP RS

4.1

Varity_R

0.067

gMVP

0.052

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

Other links and lift over