6-3153895-A-C

Position:

• chr6-3153895-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2 PP2 BP4_Moderate

The NM_001069.3(TUBB2A):​c.1306T>G​(p.Phe436Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 30)
• Consequence: TUBB2A NM_001069.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.27

Genes affected

TUBB2A (HGNC:12412): (tubulin beta 2A class IIa) Microtubules, key participants in processes such as mitosis and intracellular transport, are composed of heterodimers of alpha- and beta-tubulins. The protein encoded by this gene is a beta-tubulin. Defects in this gene are associated with complex cortical dysplasia with other brain malformations-5. Two transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Jul 2015]

TUBB2A (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant in gene, where missense usually causes diseases (based on misZ statistic), TUBB2A. . Gene score misZ 5.2633 (greater than the threshold 3.09). Trascript score misZ 6.0248 (greater than threshold 3.09). GenCC has associacion of gene with complex cortical dysplasia with other brain malformations 5, tubulinopathy.
• BP4: Computational evidence support a benign effect (MetaRNN=0.15132076).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TUBB2A	NM_001069.3	c.1306T>G	p.Phe436Val	missense_variant	4/4	ENST00000333628.4	NP_001060.1
TUBB2A	NM_001310315.2	c.1051T>G	p.Phe351Val	missense_variant	4/4		NP_001297244.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TUBB2A	ENST00000333628.4	c.1306T>G	p.Phe436Val	missense_variant	4/4	1	NM_001069.3	ENSP00000369703.2

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 30

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

GeneDx

Jan 19, 2024

Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.32
BayesDel_addAF	Uncertain	0.040	T
BayesDel_noAF	Benign	-0.18
CADD	Uncertain	25
DANN	Benign	0.95
DEOGEN2	Benign	0.19	T
Eigen	Benign	-0.12
Eigen_PC	Benign	-0.018
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.065	D
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-0.87	T
MutationAssessor	Benign	0.64	N
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-1.1	N
REVEL	Uncertain	0.34
Sift4G	Benign	0.28	T
Polyphen		0.0030	B
Vest4		0.41
MutPred		0.19		Loss of helix (P = 0.1299);
MVP		0.53
ClinPred		0.83	D
GERP RS		2.6
Varity_R		0.32
gMVP		0.90

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-3154129;