17-45983409-C-T

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.830C>T(p.Pro277Leu) 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 1,606,114 control chromosomes in the GnomAD database, including 32,668 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.14 ( 2145 hom., cov: 32)

Exomes 𝑓: 0.19 ( 30523 hom. )

Consequence

MAPT
NM_001377265.1 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6O:1

Conservation

PhyloP100: 0.432

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=0.0061332285).

BP6

Variant 17-45983409-C-T is Benign according to our data. Variant chr17-45983409-C-T is described in ClinVar as [Benign]. Clinvar id is 98244.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-45983409-C-T 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.830C>T	p.Pro277Leu	missense_variant	Exon 5 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.830C>T	p.Pro277Leu	missense_variant	Exon 5 of 13	1	NM_001377265.1	ENSP00000262410.6		A0A7I2PJZ2

Frequencies

GnomAD3 genomes

AF:

0.145

AC:

22080

AN:

152104

Hom.:

2147

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0492

Gnomad AMI

AF:

0.277

Gnomad AMR

AF:

0.176

Gnomad ASJ

AF:

0.240

Gnomad EAS

AF:

0.00154

Gnomad SAS

AF:

0.0738

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:

35042

AN:

239580

Hom.:

3423

AF XY:

0.150

AC XY:

19601

AN XY:

130826

show subpopulations

Gnomad AFR exome

AF:

0.0481

Gnomad AMR exome

AF:

0.119

Gnomad ASJ exome

AF:

0.257

Gnomad EAS exome

AF:

0.000661

Gnomad SAS exome

AF:

0.0765

Gnomad FIN exome

AF:

0.0691

Gnomad NFE exome

AF:

0.217

Gnomad OTH exome

AF:

0.178

GnomAD4 exome

AF:

0.194

AC:

281770

AN:

1453892

Hom.:

30523

Cov.:

AF XY:

0.191

AC XY:

138180

AN XY:

722234

show subpopulations

Gnomad4 AFR exome

AF:

0.0430

Gnomad4 AMR exome

AF:

0.125

Gnomad4 ASJ exome

AF:

0.256

Gnomad4 EAS exome

AF:

0.000885

Gnomad4 SAS exome

AF:

0.0798

Gnomad4 FIN exome

AF:

0.0725

Gnomad4 NFE exome

AF:

0.222

Gnomad4 OTH exome

AF:

0.177

GnomAD4 genome

AF:

0.145

AC:

22070

AN:

152222

Hom.:

2145

Cov.:

AF XY:

0.136

AC XY:

10132

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.0491

Gnomad4 AMR

AF:

0.176

Gnomad4 ASJ

AF:

0.240

Gnomad4 EAS

AF:

0.00154

Gnomad4 SAS

AF:

0.0738

Gnomad4 FIN

AF:

0.0652

Gnomad4 NFE

AF:

0.217

Gnomad4 OTH

AF:

0.183

Alfa

AF:

0.200

Hom.:

1262

Bravo

AF:

0.150

TwinsUK

AF:

0.233

AC:

864

ALSPAC

AF:

0.241

AC:

929

ESP6500AA

AF:

0.0510

AC:

220

ESP6500EA

AF:

0.222

AC:

1886

ExAC

AF:

0.144

AC:

17428

Asia WGS

AF:

0.0310

AC:

111

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

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

- -

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided

Benign:2Other:1

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: 30679340, 23222517) -

VIB Department of Molecular Genetics, University of Antwerp

Significance: not provided

Review Status: no classification provided

Collection Method: literature only

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Frontotemporal dementia

Benign:1

Jan 14, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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

0.069

BayesDel_addAF

Benign

-0.75

BayesDel_noAF

Benign

-0.71

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.30

T;.;.;T

Eigen

Benign

-0.53

Eigen_PC

Benign

-0.76

FATHMM_MKL

Benign

0.026

LIST_S2

Benign

0.65

T;T;.;.

MetaRNN

Benign

0.0061

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.0

L;L;L;L

PrimateAI

Benign

0.36

PROVEAN

Benign

-1.1

N;N;N;.

REVEL

Benign

0.030

Sift

Pathogenic

0.0

D;D;D;.

Sift4G

Uncertain

0.0080

D;D;D;D

Polyphen

1.0

D;D;D;D

Vest4

0.11

MPC

0.16

ClinPred

0.012

GERP RS

-0.93

Varity_R

0.049

gMVP

0.11

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.

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