NM_001377265.1(MAPT):c.1568G>A (p.Arg523Gln) AND Semantic dementia

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jan 5, 2024
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV003994604.1

Allele description [Variation Report for NM_001377265.1(MAPT):c.1568G>A (p.Arg523Gln)]

NM_001377265.1(MAPT):c.1568G>A (p.Arg523Gln)

Gene:

MAPT:microtubule associated protein tau [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

17q21.31

Genomic location:

Preferred name:

NM_001377265.1(MAPT):c.1568G>A (p.Arg523Gln)

HGVS:

NC_000017.11:g.45990038G>A
NG_007398.2:g.100576G>A
NM_001123066.4:c.1343G>A
NM_001123067.4:c.343-1422G>A
NM_001203251.2:c.343-1422G>A
NM_001203252.2:c.430-1422G>A
NM_001377265.1:c.1568G>AMANE SELECT
NM_001377266.1:c.1408-1422G>A
NM_001377267.1:c.343-1422G>A
NM_001377268.1:c.256-1422G>A
NM_005910.6:c.430-1422G>A
NM_016834.5:c.256-1422G>A
NM_016835.5:c.1343G>A
NM_016841.5:c.256-1422G>A
NP_001116538.2:p.Arg448Gln
NP_001364194.1:p.Arg523Gln
NP_058519.3:p.Arg448Gln
LRG_660t1:c.1343G>A
LRG_660t2:c.1568G>A
LRG_660:g.100576G>A
LRG_660p1:p.Arg448Gln
LRG_660p2:p.Arg523Gln
NC_000017.10:g.44067404G>A
NM_001123066.3:c.1343G>A

Protein change:

R448Q

Molecular consequence:

NM_001123067.4:c.343-1422G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001203251.2:c.343-1422G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001203252.2:c.430-1422G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001377266.1:c.1408-1422G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001377267.1:c.343-1422G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001377268.1:c.256-1422G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_005910.6:c.430-1422G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_016834.5:c.256-1422G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_016841.5:c.256-1422G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001123066.4:c.1343G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001377265.1:c.1568G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_016835.5:c.1343G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Semantic dementia
Identifiers:: MONDO: MONDO:0010857; MedGen: C0338462; Human Phenotype Ontology: HP:0030219

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004812528	Molecular Genetics, Royal Melbourne Hospital See additional submitters Shariant Australia, Australian Genomics	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Jan 5, 2024)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004812528

Molecular Genetics, Royal Melbourne Hospital

See additional submitters

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Jan 5, 2024)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Molecular Genetics, Royal Melbourne Hospital, SCV004812528.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

This sequence change in MAPT is predicted to replace arginine with glutamine at codon 523, p.(Arg523Gln). The arginine residue is moderately conserved (100 vertebrates, UCSC). There is a small physicochemical difference between arginine and glutamine. The highest population minor allele frequency in the population database gnomAD v4.0 is 0.005% (59/1,180,038 alleles) in the European non-Finnish population. To our knowledge, this variant has not been previously reported in the relevant scientific literature or databases. Computational evidence predicts a benign effect for the missense substitution (REVEL = 0.07). Based on the classification scheme RMH Modified ACMG/AMP Guidelines v1.6.1, this variant is classified as a VARIANT OF UNCERTAIN SIGNIFICANCE. Following criteria are met: BP4

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Oct 13, 2024

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