NM_001377265.1:c.1623G>A

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS1

The NM_001377265.1(MAPT):​c.1623G>A​(p.Thr541Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00017 in 1,614,094 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00018 ( 0 hom. )

Consequence

MAPT
NM_001377265.1 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.36

Publications

1 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

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.46).
BP6
Variant 17-45991477-G-A is Benign according to our data. Variant chr17-45991477-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 460295.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-1.36 with no splicing effect.
BS1
Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0000788 (12/152208) while in subpopulation NFE AF = 0.000147 (10/68030). AF 95% confidence interval is 0.0000791. There are 0 homozygotes in GnomAd4. There are 3 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MAPTNM_001377265.1 linkc.1623G>A p.Thr541Thr synonymous_variant Exon 8 of 13 ENST00000262410.10 NP_001364194.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MAPTENST00000262410.10 linkc.1623G>A p.Thr541Thr synonymous_variant Exon 8 of 13 1 NM_001377265.1 ENSP00000262410.6 A0A7I2PJZ2

Frequencies

GnomAD3 genomes
AF:
0.0000788
AC:
12
AN:
152208
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000483
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000147
Gnomad OTH
AF:
0.00
GnomAD2 exomes
AF:
0.0000955
AC:
24
AN:
251294
AF XY:
0.000103
show subpopulations
Gnomad AFR exome
AF:
0.0000616
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000194
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000179
AC:
262
AN:
1461886
Hom.:
0
Cov.:
32
AF XY:
0.000175
AC XY:
127
AN XY:
727244
show subpopulations
African (AFR)
AF:
0.0000299
AC:
1
AN:
33480
American (AMR)
AF:
0.0000224
AC:
1
AN:
44724
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26136
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39700
South Asian (SAS)
AF:
0.0000348
AC:
3
AN:
86258
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53416
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
0.000219
AC:
244
AN:
1112008
Other (OTH)
AF:
0.000215
AC:
13
AN:
60396
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.482
Heterozygous variant carriers
0
16
32
48
64
80
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
10
20
30
40
50
<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:
0.0000788
AC:
12
AN:
152208
Hom.:
0
Cov.:
32
AF XY:
0.0000403
AC XY:
3
AN XY:
74368
show subpopulations
African (AFR)
AF:
0.0000483
AC:
2
AN:
41446
American (AMR)
AF:
0.00
AC:
0
AN:
15284
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3472
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5196
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4832
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10626
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
0.000147
AC:
10
AN:
68030
Other (OTH)
AF:
0.00
AC:
0
AN:
2094
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.508
Heterozygous variant carriers
0
1
2
3
4
5
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
2
4
6
8
10
<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:
0.000263
Hom.:
0
Bravo
AF:
0.000117
EpiCase
AF:
0.000109
EpiControl
AF:
0.000119

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Frontotemporal dementia Benign:1
Dec 31, 2022
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Likely 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
-0.46
CADD
Benign
5.8
DANN
Benign
0.71
PhyloP100
-1.4

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

Other links and lift over

dbSNP: rs139748238; hg19: chr17-44068843; COSMIC: COSV52238377; COSMIC: COSV52238377; API