rs62063786

Positions:

chr17-45983657-G-A

Variant summary

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

The NM_001377265.1(MAPT):c.1078G>A(p.Asp360Asn) 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 1,613,904 control chromosomes in the GnomAD database, including 32,809 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 (★★). Synonymous variant affecting the same amino acid position (i.e. D360D) has been classified as Benign.

Frequency

Genomes: 𝑓 0.14 ( 2142 hom., cov: 33)

Exomes 𝑓: 0.19 ( 30667 hom. )

Consequence

MAPT
NM_001377265.1 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.00700

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:

MAPT (HGNC:):

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=0.0051706433).

BP6

Variant 17-45983657-G-A is Benign according to our data. Variant chr17-45983657-G-A is described in ClinVar as [Benign]. Clinvar id is 98198.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-45983657-G-A 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/exons	MANE	Protein	UniProt
MAPT	NM_001377265.1 linkuse as main transcript	c.1078G>A	p.Asp360Asn	missense_variant	5/13	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.1078G>A	p.Asp360Asn	missense_variant	5/13	1	NM_001377265.1	ENSP00000262410.6		A0A7I2PJZ2

Frequencies

GnomAD3 genomes

AF:

0.145

AC:

22081

AN:

152124

Hom.:

2144

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0494

Gnomad AMI

AF:

0.277

Gnomad AMR

AF:

0.176

Gnomad ASJ

AF:

0.240

Gnomad EAS

AF:

0.00155

Gnomad SAS

AF:

0.0740

Gnomad FIN

AF:

0.0651

Gnomad MID

AF:

0.218

Gnomad NFE

AF:

0.217

Gnomad OTH

AF:

0.186

GnomAD3 exomes

AF:

0.146

AC:

36521

AN:

250866

Hom.:

3542

AF XY:

0.149

AC XY:

20234

AN XY:

135770

show subpopulations

Gnomad AFR exome

AF:

0.0474

Gnomad AMR exome

AF:

0.119

Gnomad ASJ exome

AF:

0.255

Gnomad EAS exome

AF:

0.000653

Gnomad SAS exome

AF:

0.0761

Gnomad FIN exome

AF:

0.0680

Gnomad NFE exome

AF:

0.213

Gnomad OTH exome

AF:

0.175

GnomAD4 exome

AF:

0.194

AC:

283018

AN:

1461662

Hom.:

30667

Cov.:

AF XY:

0.191

AC XY:

139000

AN XY:

727122

show subpopulations

Gnomad4 AFR exome

AF:

0.0431

Gnomad4 AMR exome

AF:

0.126

Gnomad4 ASJ exome

AF:

0.256

Gnomad4 EAS exome

AF:

0.000907

Gnomad4 SAS exome

AF:

0.0796

Gnomad4 FIN exome

AF:

0.0725

Gnomad4 NFE exome

AF:

0.222

Gnomad4 OTH exome

AF:

0.177

GnomAD4 genome

AF:

0.145

AC:

22071

AN:

152242

Hom.:

2142

Cov.:

AF XY:

0.136

AC XY:

10121

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.0493

Gnomad4 AMR

AF:

0.176

Gnomad4 ASJ

AF:

0.240

Gnomad4 EAS

AF:

0.00155

Gnomad4 SAS

AF:

0.0741

Gnomad4 FIN

AF:

0.0651

Gnomad4 NFE

AF:

0.217

Gnomad4 OTH

AF:

0.183

Alfa

AF:

0.205

Hom.:

5664

Bravo

AF:

0.150

TwinsUK

AF:

0.232

AC:

861

ALSPAC

AF:

0.241

AC:

928

ESP6500AA

AF:

0.0517

AC:

228

ESP6500EA

AF:

0.224

AC:

1928

ExAC

AF:

0.145

AC:

17580

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

Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, Amsterdam University Medical Center	-	- -

not provided

Benign:2Other:1

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
not provided, no classification provided	literature only	VIB Department of Molecular Genetics, University of Antwerp	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 11, 2018	This variant is associated with the following publications: (PMID: 23222517) -

Frontotemporal dementia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 19, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.83

BayesDel_noAF

Benign

-0.82

CADD

Benign

4.8

DANN

Uncertain

0.98

DEOGEN2

Benign

0.30

T;.;.;T

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.026

LIST_S2

Benign

0.19

T;T;.;.

MetaRNN

Benign

0.0052

T;T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.3

L;L;L;L

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.86

N;N;N;.

REVEL

Benign

0.035

Sift

Uncertain

0.015

D;D;D;.

Sift4G

Benign

0.39

T;T;T;T

Polyphen

0.15

B;B;B;B

Vest4

0.047

MPC

0.15

ClinPred

0.0018

GERP RS

-3.2

Varity_R

0.052

gMVP

0.078

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