chr17-45894659-TC-T

Position:

• chr17-45894659-TC-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001377265.1(MAPT):​c.-42del 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

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

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
MAPT	NM_001377265.1	c.-42del		5_prime_UTR_variant	1/13	ENST00000262410.10
MAPT-AS1	NR_024559.1	n.34+820del		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAPT	ENST00000262410.10	c.-42del		5_prime_UTR_variant	1/13	1	NM_001377265.1	A2
MAPT-AS1	ENST00000634876.2	n.182+820del		intron_variant, non_coding_transcript_variant		5

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

Gnomad4 AFR exome AF: 0.0455

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.167

Gnomad4 EAS exome AF: 0.0161

Gnomad4 SAS exome AF: 0.0676

Gnomad4 FIN exome AF: 0.0833

Gnomad4 NFE exome AF: 0.131

Gnomad4 OTH exome AF: 0.0811

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

Gnomad4 AFR AF: 0.0392

Gnomad4 AMR AF: 0.175

Gnomad4 ASJ AF: 0.241

Gnomad4 EAS AF: 0.00156

Gnomad4 SAS AF: 0.0745

Gnomad4 FIN AF: 0.0651

Gnomad4 NFE AF: 0.217

Gnomad4 OTH AF: 0.179

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

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs144722105; hg19: chr17-43972025;