rs11568305

Positions:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001377265.1(MAPT):c.1986G>A(p.Pro662Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.041 in 1,613,756 control chromosomes in the GnomAD database, including 1,538 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.039 ( 120 hom., cov: 32)

Exomes 𝑓: 0.041 ( 1418 hom. )

Consequence

MAPT
NM_001377265.1 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10O:1

Conservation

PhyloP100: -3.86

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP6

Variant 17-45996652-G-A is Benign according to our data. Variant chr17-45996652-G-A is described in ClinVar as [Benign]. Clinvar id is 98211.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-45996652-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-3.86 with no splicing effect.

BA1

GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.104 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.1986G>A	p.Pro662Pro	synonymous_variant	9/13	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.1986G>A	p.Pro662Pro	synonymous_variant	9/13	1	NM_001377265.1	ENSP00000262410.6		A0A7I2PJZ2

Frequencies

GnomAD3 genomes

AF:

0.0388

AC:

5900

AN:

152108

Hom.:

119

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0346

Gnomad AMI

AF:

0.0702

Gnomad AMR

AF:

0.0367

Gnomad ASJ

AF:

0.0461

Gnomad EAS

AF:

0.0154

Gnomad SAS

AF:

0.0383

Gnomad FIN

AF:

0.0239

Gnomad MID

AF:

0.123

Gnomad NFE

AF:

0.0444

Gnomad OTH

AF:

0.0508

GnomAD3 exomes

AF:

0.0352

AC:

8719

AN:

247630

Hom.:

190

AF XY:

0.0367

AC XY:

4930

AN XY:

134424

show subpopulations

Gnomad AFR exome

AF:

0.0328

Gnomad AMR exome

AF:

0.0221

Gnomad ASJ exome

AF:

0.0474

Gnomad EAS exome

AF:

0.0157

Gnomad SAS exome

AF:

0.0403

Gnomad FIN exome

AF:

0.0231

Gnomad NFE exome

AF:

0.0419

Gnomad OTH exome

AF:

0.0504

GnomAD4 exome

AF:

0.0412

AC:

60185

AN:

1461530

Hom.:

1418

Cov.:

AF XY:

0.0415

AC XY:

30148

AN XY:

727040

show subpopulations

Gnomad4 AFR exome

AF:

0.0370

Gnomad4 AMR exome

AF:

0.0238

Gnomad4 ASJ exome

AF:

0.0454

Gnomad4 EAS exome

AF:

0.0166

Gnomad4 SAS exome

AF:

0.0414

Gnomad4 FIN exome

AF:

0.0256

Gnomad4 NFE exome

AF:

0.0430

Gnomad4 OTH exome

AF:

0.0445

GnomAD4 genome

AF:

0.0388

AC:

5903

AN:

152226

Hom.:

120

Cov.:

AF XY:

0.0382

AC XY:

2840

AN XY:

74424

show subpopulations

Gnomad4 AFR

AF:

0.0346

Gnomad4 AMR

AF:

0.0366

Gnomad4 ASJ

AF:

0.0461

Gnomad4 EAS

AF:

0.0155

Gnomad4 SAS

AF:

0.0389

Gnomad4 FIN

AF:

0.0239

Gnomad4 NFE

AF:

0.0444

Gnomad4 OTH

AF:

0.0502

Alfa

AF:

0.0386

Hom.:

Bravo

AF:

0.0396

Asia WGS

AF:

0.0310

AC:

109

AN:

3478

EpiCase

AF:

0.0467

EpiControl

AF:

0.0433

ClinVar

Significance: Benign

Submissions summary: Benign:10Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:6

Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Feb 25, 2011	- -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
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	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, Amsterdam University Medical Center	-	- -

not provided

Benign:2Other:1

not provided, no classification provided	literature only	VIB Department of Molecular Genetics, University of Antwerp	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 08, 2021	This variant is associated with the following publications: (PMID: 12826737, 26159191, 18854867, 19091059, 9973279, 20020531, 16410051, 25671699) -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

MAPT-Related Spectrum Disorders

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Frontotemporal dementia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 30, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

0.16

DANN

Benign

0.86

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