rs16940758

Variant names:

• chr17-45963260-C-T
• rs16940758
• NM_001377265.1:c.133+790C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001377265.1(MAPT):​c.133+790C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.195 in 152,168 control chromosomes in the GnomAD database, including 2,987 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.20 (2987 hom., cov: 32)
• Consequence: MAPT NM_001377265.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0750
• Publications: 12 publications found

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):

• late-onset Parkinson disease

  Inheritance: AD, Unknown Classification: STRONG, LIMITED Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
• Pick disease

  Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
• semantic dementia

  Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp
• supranuclear palsy, progressive, 1

  Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp
• progressive supranuclear palsy-parkinsonism syndrome

  Inheritance: AR Classification: MODERATE, LIMITED Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.307 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001377265.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAPT	NM_001377265.1	MANE Select	c.133+790C>T		intron	N/A	NP_001364194.1	A0A7I2PJZ2
	MAPT	NM_001123066.4		c.133+790C>T		intron	N/A	NP_001116538.2	P10636-9
	MAPT	NM_016835.5		c.133+790C>T		intron	N/A	NP_058519.3	P10636-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAPT	ENST00000262410.10	TSL:1 MANE Select	c.133+790C>T		intron	N/A	ENSP00000262410.6	A0A7I2PJZ2
	MAPT	ENST00000344290.10	TSL:1	c.133+790C>T		intron	N/A	ENSP00000340820.6	A0A7I2PLE3
	MAPT	ENST00000351559.10	TSL:1	c.133+790C>T		intron	N/A	ENSP00000303214.7	P10636-8

Frequencies

GnomAD3 genomes AF: 0.195 AC: 29662 AN: 152050 Hom.: 2985 Cov.: 32

Gnomad AFR AF: 0.218

Gnomad AMI AF: 0.225

Gnomad AMR AF: 0.182

Gnomad ASJ AF: 0.153

Gnomad EAS AF: 0.181

Gnomad SAS AF: 0.319

Gnomad FIN AF: 0.195

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.177

Gnomad OTH AF: 0.229

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.195 AC: 29685 AN: 152168 Hom.: 2987 Cov.: 32 AF XY: 0.198 AC XY: 14750 AN XY: 74384

African (AFR) AF: 0.218 AC: 9039 AN: 41520

American (AMR) AF: 0.181 AC: 2771 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.153 AC: 531 AN: 3468

East Asian (EAS) AF: 0.180 AC: 931 AN: 5168

South Asian (SAS) AF: 0.320 AC: 1542 AN: 4812

European-Finnish (FIN) AF: 0.195 AC: 2069 AN: 10596

Middle Eastern (MID) AF: 0.350 AC: 103 AN: 294

European-Non Finnish (NFE) AF: 0.177 AC: 12015 AN: 68000

Other (OTH) AF: 0.227 AC: 480 AN: 2114

Alfa AF: 0.182 Hom.: 4289

Bravo AF: 0.191

Asia WGS AF: 0.233 AC: 813 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.92
DANN	Benign	0.72
PhyloP100		0.075
Mutation Taster		=100/0	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: rs16940758; hg19: chr17-44040626;