rs9468

Variant names:

• chr17-46024197-T-C
• rs9468
• NM_001377265.1:c.*26T>C

Your query was ambiguous. Multiple possible variants found:

• chr17-46024197-T-C
• chr17-46024197-T-A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001377265.1(MAPT):​c.*26T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.19 in 1,596,984 control chromosomes in the GnomAD database, including 32,639 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.14 (2145 hom., cov: 32)
  • Exomes 𝑓: 0.19 (30494 hom.)
• Consequence: MAPT NM_001377265.1 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.46
• Publications: 66 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 17-46024197-T-C is Benign according to our data. Variant chr17-46024197-T-C is described in ClinVar as Benign. ClinVar VariationId is 323650.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.215 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.*26T>C		3_prime_UTR	Exon 13 of 13	NP_001364194.1	A0A7I2PJZ2
	MAPT	NM_001123066.4		c.*26T>C		3_prime_UTR	Exon 15 of 15	NP_001116538.2	P10636-9
	MAPT	NM_016835.5		c.*26T>C		3_prime_UTR	Exon 14 of 14	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.*26T>C		3_prime_UTR	Exon 13 of 13	ENSP00000262410.6	A0A7I2PJZ2
	MAPT	ENST00000344290.10	TSL:1	c.*26T>C		3_prime_UTR	Exon 11 of 11	ENSP00000340820.6	A0A7I2PLE3
	MAPT	ENST00000351559.10	TSL:1	c.*26T>C		3_prime_UTR	Exon 12 of 12	ENSP00000303214.7	P10636-8

Frequencies

GnomAD3 genomes AF: 0.144 AC: 21882 AN: 151782 Hom.: 2147 Cov.: 32

Gnomad AFR AF: 0.0407

Gnomad AMI AF: 0.277

Gnomad AMR AF: 0.176

Gnomad ASJ AF: 0.240

Gnomad EAS AF: 0.00155

Gnomad SAS AF: 0.0742

Gnomad FIN AF: 0.0802

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.217

Gnomad OTH AF: 0.185

GnomAD2 exomes AF: 0.146 AC: 36449 AN: 248996 AF XY: 0.150

Gnomad AFR exome AF: 0.0379

Gnomad AMR exome AF: 0.119

Gnomad ASJ exome AF: 0.254

Gnomad EAS exome AF: 0.000655

Gnomad FIN exome AF: 0.0812

Gnomad NFE exome AF: 0.214

Gnomad OTH exome AF: 0.176

GnomAD4 exome AF: 0.195 AC: 281126 AN: 1445084 Hom.: 30494 Cov.: 28 AF XY: 0.192 AC XY: 138276 AN XY: 720062

African (AFR) AF: 0.0345 AC: 1140 AN: 33026

American (AMR) AF: 0.125 AC: 5604 AN: 44662

Ashkenazi Jewish (ASJ) AF: 0.257 AC: 6678 AN: 26028

East Asian (EAS) AF: 0.000884 AC: 35 AN: 39608

South Asian (SAS) AF: 0.0796 AC: 6837 AN: 85916

European-Finnish (FIN) AF: 0.0859 AC: 4554 AN: 52998

Middle Eastern (MID) AF: 0.202 AC: 1154 AN: 5714

European-Non Finnish (NFE) AF: 0.223 AC: 244498 AN: 1097272

Other (OTH) AF: 0.178 AC: 10626 AN: 59860

GnomAD4 genome AF: 0.144 AC: 21870 AN: 151900 Hom.: 2145 Cov.: 32 AF XY: 0.135 AC XY: 10048 AN XY: 74266

African (AFR) AF: 0.0405 AC: 1680 AN: 41434

American (AMR) AF: 0.176 AC: 2686 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.240 AC: 832 AN: 3468

East Asian (EAS) AF: 0.00155 AC: 8 AN: 5156

South Asian (SAS) AF: 0.0742 AC: 357 AN: 4810

European-Finnish (FIN) AF: 0.0802 AC: 847 AN: 10556

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.217 AC: 14761 AN: 67886

Other (OTH) AF: 0.182 AC: 383 AN: 2106

Alfa AF: 0.177 Hom.: 1197

Bravo AF: 0.147

Asia WGS AF: 0.0300 AC: 106 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	MAPT-Related Spectrum Disorders (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	9.5
DANN	Benign	0.63
PhyloP100		1.5
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: rs9468; hg19: chr17-44101563;