17-45962387-C-T

Position:

chr17-45962387-C-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS1

The NM_001377265.1(MAPT):c.50C>T(p.Thr17Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000154 in 1,612,588 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00076 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000092 ( 1 hom. )

Consequence

MAPT
NM_001377265.1 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.353

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 -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.011078745).

BP6

Variant 17-45962387-C-T is Benign according to our data. Variant chr17-45962387-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 704535.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-45962387-C-T is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000756 (115/152176) while in subpopulation AFR AF= 0.0027 (112/41528). AF 95% confidence interval is 0.00229. There are 0 homozygotes in gnomad4. There are 57 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAPT	NM_001377265.1 linkuse as main transcript	c.50C>T	p.Thr17Met	missense_variant	2/13	ENST00000262410.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAPT	ENST00000262410.10 linkuse as main transcript	c.50C>T	p.Thr17Met	missense_variant	2/13	1	NM_001377265.1	A2

Frequencies

GnomAD3 genomes

AF:

0.000756

AC:

115

AN:

152058

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00270

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000195

AC:

AN:

251100

Hom.:

AF XY:

0.000133

AC XY:

AN XY:

135722

show subpopulations

Gnomad AFR exome

AF:

0.00271

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000918

AC:

134

AN:

1460412

Hom.:

Cov.:

AF XY:

0.0000826

AC XY:

AN XY:

726520

show subpopulations

Gnomad4 AFR exome

AF:

0.00290

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000504

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000270

Gnomad4 OTH exome

AF:

0.000199

GnomAD4 genome

AF:

0.000756

AC:

115

AN:

152176

Hom.:

Cov.:

AF XY:

0.000766

AC XY:

AN XY:

74402

show subpopulations

Gnomad4 AFR

AF:

0.00270

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000124

Hom.:

Bravo

AF:

0.000790

ESP6500AA

AF:

0.00340

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000214

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Frontotemporal dementia

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Oct 07, 2022

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 11, 2020

This variant is associated with the following publications: (PMID: 25174650, 20020531) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.32

T;.;.;.;.;.;.;.;.;T;.;.

Eigen

Benign

-0.42

Eigen_PC

Benign

-0.60

FATHMM_MKL

Benign

0.024

LIST_S2

Benign

0.83

T;T;T;T;D;T;T;.;.;.;.;.

M_CAP

Benign

0.020

MetaRNN

Benign

0.011

T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.0

L;L;L;L;L;L;L;L;L;L;L;L

MutationTaster

Benign

1.0

N;N;N;N;N;N;N;N;N;N;N;N;N

PrimateAI

Benign

0.38

PROVEAN

Benign

-0.69

N;N;N;N;N;N;N;N;N;.;.;.

REVEL

Benign

0.098

Sift

Uncertain

0.011

D;D;D;D;D;T;T;D;D;.;.;.

Sift4G

Uncertain

0.032

D;T;D;T;T;T;T;T;D;D;T;T

Polyphen

0.99

D;D;D;.;D;P;P;D;D;D;D;.

Vest4

0.12

MVP

0.58

MPC

0.40

ClinPred

0.078

GERP RS

0.52

Varity_R

0.11

gMVP

0.033

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