chr17-45983659-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001377265.1(MAPT):c.1080C>T(p.Asp360Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 1,613,920 control chromosomes in the GnomAD database, including 12,181 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.11 ( 976 hom., cov: 33)

Exomes 𝑓: 0.12 ( 11205 hom. )

Consequence

MAPT
NM_001377265.1 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -4.11

Publications

25 publications found

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 Gene-Disease associations (from GenCC):

Pick disease
Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp
semantic dementia
Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp
supranuclear palsy, progressive, 1
Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp
late-onset Parkinson disease
Inheritance: Unknown, AD Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp
progressive supranuclear palsy-parkinsonism syndrome
Inheritance: AR Classification: MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp

MAPT links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 17-45983659-C-T is Benign according to our data. Variant chr17-45983659-C-T is described in ClinVar as Benign. ClinVar VariationId is 98199.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-4.11 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.189 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAPT	NM_001377265.1 link	c.1080C>T	p.Asp360Asp	synonymous_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.1080C>T	p.Asp360Asp	synonymous_variant	Exon 5 of 13	1	NM_001377265.1	ENSP00000262410.6		A0A7I2PJZ2

Frequencies

GnomAD3 genomes

AF:

0.107

AC:

16238

AN:

152122

Hom.:

973

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0455

Gnomad AMI

AF:

0.0581

Gnomad AMR

AF:

0.147

Gnomad ASJ

AF:

0.105

Gnomad EAS

AF:

0.199

Gnomad SAS

AF:

0.0845

Gnomad FIN

AF:

0.164

Gnomad MID

AF:

0.0981

Gnomad NFE

AF:

0.121

Gnomad OTH

AF:

0.0994

GnomAD2 exomes

AF:

0.128

AC:

32151

AN:

250932

AF XY:

0.124

show subpopulations

Gnomad AFR exome

AF:

0.0397

Gnomad AMR exome

AF:

0.198

Gnomad ASJ exome

AF:

0.0912

Gnomad EAS exome

AF:

0.209

Gnomad FIN exome

AF:

0.164

Gnomad NFE exome

AF:

0.119

Gnomad OTH exome

AF:

0.125

GnomAD4 exome

AF:

0.120

AC:

175487

AN:

1461680

Hom.:

11205

Cov.:

AF XY:

0.119

AC XY:

86526

AN XY:

727126

show subpopulations

African (AFR)

AF:

0.0379

AC:

1270

AN:

33480

American (AMR)

AF:

0.193

AC:

8639

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.0948

AC:

2477

AN:

26132

East Asian (EAS)

AF:

0.173

AC:

6878

AN:

39700

South Asian (SAS)

AF:

0.0754

AC:

6504

AN:

86256

European-Finnish (FIN)

AF:

0.164

AC:

8744

AN:

53272

Middle Eastern (MID)

AF:

0.0747

AC:

431

AN:

5768

European-Non Finnish (NFE)

AF:

0.120

AC:

133493

AN:

1111962

Other (OTH)

AF:

0.117

AC:

7051

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

9994

19988

29982

39976

49970

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4904

9808

14712

19616

24520

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.107

AC:

16246

AN:

152240

Hom.:

976

Cov.:

AF XY:

0.109

AC XY:

8140

AN XY:

74438

show subpopulations

African (AFR)

AF:

0.0455

AC:

1890

AN:

41574

American (AMR)

AF:

0.148

AC:

2265

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.105

AC:

365

AN:

3470

East Asian (EAS)

AF:

0.199

AC:

1026

AN:

5148

South Asian (SAS)

AF:

0.0848

AC:

409

AN:

4824

European-Finnish (FIN)

AF:

0.164

AC:

1743

AN:

10596

Middle Eastern (MID)

AF:

0.102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.121

AC:

8256

AN:

67998

Other (OTH)

AF:

0.0989

AC:

209

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

758

1515

2273

3030

3788

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

186

372

558

744

930

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0985

Hom.:

450

Bravo

AF:

0.104

Asia WGS

AF:

0.167

AC:

577

AN:

3478

EpiCase

AF:

0.115

EpiControl

AF:

0.113

ClinVar

Significance: Benign

Submissions summary: Benign:6Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Clinical Genetics, Academic Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

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

- -

not provided

Benign:2Other:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Aug 15, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

VIB Department of Molecular Genetics, University of Antwerp

Significance:not provided

Review Status:no classification provided

Collection Method:literature only

- -

Frontotemporal dementia

Benign:1

Jan 06, 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

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.51

(source)

DANN

Benign

0.49

PhyloP100

-4.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over