17-45894659-TC-T

Variant names:

• chr17-45894659-TC-T
• rs144722105
• ENST00000579599.1:n.854delG

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001377265.1(MAPT):​c.-42delC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.142 in 153,352 control chromosomes in the GnomAD database, including 2,133 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.14 (2121 hom., cov: 29)
  • Exomes 𝑓: 0.11 (12 hom.)
• Consequence: MAPT NM_001377265.1 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.06
• Publications: 7 publications found

Genes affected

MAPT-AS1 (HGNC:43738): (MAPT antisense RNA 1) Implicated in Parkinson's disease. [provided by Alliance of Genome Resources, Apr 2022]

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

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 17-45894659-TC-T is Benign according to our data. Variant chr17-45894659-TC-T is described in ClinVar as [Benign]. Clinvar id is 323640.Status of the report is criteria_provided_single_submitter, 1 stars.
• 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 rank	MANE	Protein	UniProt
MAPT	NM_001377265.1	c.-42delC		5_prime_UTR_variant	Exon 1 of 13	ENST00000262410.10	NP_001364194.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAPT	ENST00000262410.10	c.-42delC		5_prime_UTR_variant	Exon 1 of 13	1	NM_001377265.1	ENSP00000262410.6

Frequencies

GnomAD3 genomes AF: 0.143 AC: 21643 AN: 151774 Hom.: 2123 Cov.: 29

Gnomad AFR AF: 0.0394

Gnomad AMI AF: 0.278

Gnomad AMR AF: 0.176

Gnomad ASJ AF: 0.241

Gnomad EAS AF: 0.00156

Gnomad SAS AF: 0.0744

Gnomad FIN AF: 0.0651

Gnomad MID AF: 0.226

Gnomad NFE AF: 0.217

Gnomad OTH AF: 0.182

GnomAD4 exome AF: 0.115 AC: 168 AN: 1464 Hom.: 12 Cov.: 0 AF XY: 0.119 AC XY: 128 AN XY: 1080

African (AFR) AF: 0.0455 AC: 1 AN: 22

American (AMR) AF: 0.00 AC: 0 AN: 8

Ashkenazi Jewish (ASJ) AF: 0.167 AC: 2 AN: 12

East Asian (EAS) AF: 0.0161 AC: 1 AN: 62

South Asian (SAS) AF: 0.0676 AC: 5 AN: 74

European-Finnish (FIN) AF: 0.0833 AC: 16 AN: 192

Middle Eastern (MID) AF: 0.500 AC: 4 AN: 8

European-Non Finnish (NFE) AF: 0.131 AC: 133 AN: 1012

Other (OTH) AF: 0.0811 AC: 6 AN: 74

GnomAD4 genome AF: 0.142 AC: 21631 AN: 151888 Hom.: 2121 Cov.: 29 AF XY: 0.133 AC XY: 9892 AN XY: 74262

African (AFR) AF: 0.0392 AC: 1626 AN: 41464

American (AMR) AF: 0.175 AC: 2678 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.241 AC: 834 AN: 3466

East Asian (EAS) AF: 0.00156 AC: 8 AN: 5126

South Asian (SAS) AF: 0.0745 AC: 359 AN: 4822

European-Finnish (FIN) AF: 0.0651 AC: 690 AN: 10592

Middle Eastern (MID) AF: 0.222 AC: 64 AN: 288

European-Non Finnish (NFE) AF: 0.217 AC: 14743 AN: 67862

Other (OTH) AF: 0.179 AC: 377 AN: 2102

Alfa AF: 0.164 Hom.: 295

Bravo AF: 0.147

Asia WGS AF: 0.0290 AC: 103 AN: 3474

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

MAPT-Related Spectrum Disorders Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-1.1
Mutation Taster		=300/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs144722105; hg19: chr17-43972025;