NM_006009.4(TUBA1A):c.421T>G (p.Phe141Val) AND Lissencephaly due to TUBA1A mutation

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: May 22, 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:: RCV004556134.1

Allele description [Variation Report for NM_006009.4(TUBA1A):c.421T>G (p.Phe141Val)]

NM_006009.4(TUBA1A):c.421T>G (p.Phe141Val)

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.421T>G (p.Phe141Val)

Other names:

NM_001270400.2:c.316T>G

HGVS:

NC_000012.12:g.49185945A>C
NG_008966.1:g.8134T>G
NM_001270399.2:c.421T>G
NM_001270400.2:c.316T>G
NM_006009.4:c.421T>GMANE SELECT
NP_001257328.1:p.Phe141Val
NP_001257329.1:p.Phe106Val
NP_006000.2:p.Phe141Val
NC_000012.11:g.49579728A>C

Protein change:

F106V

Molecular consequence:

NM_001270399.2:c.421T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001270400.2:c.316T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_006009.4:c.421T>G - 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
SCV005045261	Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain Significance (May 22, 2024)	germline	curation	PubMed (1) [See all records that cite this PMID] Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV005045261

Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain Significance
(May 22, 2024)

germline

curation

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

Citation Link

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	curation

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 Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard, SCV005045261.1

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

Description

The heterozygous p.Phe141Val variant in TUBA1A was identified by our study in one individual with lissencephaly 3. Trio exome analysis showed this variant to be de novo. The variant has not been previously reported in individuals with lissencephaly 3, and was absent from large population studies. Computational prediction tools and conservation analyses suggest that this variant may impact the protein, though this information is not predictive enough to determine pathogenicity. The number of missense variants reported in TUBA1A in the general population is lower than expected, suggesting there is little benign variation in this gene and slightly increasing the possibility that a missense variant in this gene may not be tolerated. In summary, the clinical significance of the p.Phe141Val variant is uncertain. ACMG/AMP Criteria applied: PS2_Supporting, PM2_Supporting, PP3, PP2 (Richards 2015).

#	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: Jun 2, 2024

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