NM_006009.4(TUBA1A):c.859T>A (p.Ser287Thr) AND Lissencephaly due to TUBA1A mutation

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Nov 11, 2021
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV002495987.3

Allele description [Variation Report for NM_006009.4(TUBA1A):c.859T>A (p.Ser287Thr)]

NM_006009.4(TUBA1A):c.859T>A (p.Ser287Thr)

Gene:

TUBA1A:tubulin alpha 1a [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

12q13.12

Genomic location:

Preferred name:

NM_006009.4(TUBA1A):c.859T>A (p.Ser287Thr)

HGVS:

NC_000012.12:g.49185507A>T
NG_008966.1:g.8572T>A
NM_001270399.2:c.859T>A
NM_001270400.2:c.754T>A
NM_006009.4:c.859T>AMANE SELECT
NP_001257328.1:p.Ser287Thr
NP_001257329.1:p.Ser252Thr
NP_006000.2:p.Ser287Thr
NC_000012.11:g.49579290A>T
NM_001270399.1:c.859T>A
NM_006009.3:c.859T>A

Protein change:

S252T

Links:

dbSNP: rs150978489

NCBI 1000 Genomes Browser:

rs150978489

Molecular consequence:

NM_001270399.2:c.859T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001270400.2:c.754T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_006009.4:c.859T>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Lissencephaly due to TUBA1A mutation (LIS3)
Synonyms:: Lissencephaly 3
Identifiers:: MONDO: MONDO:0012703; MedGen: C4305153; Orphanet: 171680; OMIM: 611603

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002783027	Fulgent Genetics, Fulgent Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Nov 11, 2021)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002820247	Neuberg Centre For Genomic Medicine, NCGM	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance	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

SCV002783027

Fulgent Genetics, Fulgent Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Nov 11, 2021)

unknown

clinical testing

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

SCV002820247

Neuberg Centre For Genomic Medicine, NCGM

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance

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	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	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 Fulgent Genetics, Fulgent Genetics, SCV002783027.1

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

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

From Neuberg Centre For Genomic Medicine, NCGM, SCV002820247.1

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

Description

The missense variant c.859T>A(p.Ser287Thr) in TUBA1A gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The variant is reported with the allele frequency (0.004%) in the gnomad and novel in 1000 genome database. The amino acid Serine at position 287 is changed to a Threonine changing protein sequence and it might alter its composition and physico-chemical properties. In silico tools predict the variant to be tolerated. The residue is conserved across species. For these reasons, this variant has been classified as Uncertain Significance.

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

Last Updated: Aug 25, 2024

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