6-3153907-C-T

Position:

• chr6-3153907-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 3P and 3B. PM2 PP2 BP4 BP6_Moderate

The ENST00000333628.4(TUBB2A):​c.1294G>A​(p.Glu432Lys) 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 Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E432Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 30)
• Consequence: TUBB2A ENST00000333628.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 7.75

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 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=0.3654515).
• BP6: Variant 6-3153907-C-T is Benign according to our data. Variant chr6-3153907-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2739731.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TUBB2A	NM_001069.3	c.1294G>A	p.Glu432Lys	missense_variant	4/4	ENST00000333628.4	NP_001060.1
TUBB2A	NM_001310315.2	c.1039G>A	p.Glu347Lys	missense_variant	4/4		NP_001297244.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TUBB2A	ENST00000333628.4	c.1294G>A	p.Glu432Lys	missense_variant	4/4	1	NM_001069.3	ENSP00000369703	P1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 30

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Aug 16, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.70
BayesDel_addAF	Pathogenic	0.33	D
BayesDel_noAF	Pathogenic	0.23
CADD	Uncertain	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.24	T
Eigen	Uncertain	0.38
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Pathogenic	0.99	D
M_CAP	Uncertain	0.18	D
MetaRNN	Benign	0.37	T
MetaSVM	Benign	-0.32	T
MutationAssessor	Uncertain	2.9	M
MutationTaster	Benign	1.0	D
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	-0.95	N
REVEL	Uncertain	0.45
Sift4G	Benign	0.091	T
Polyphen		0.57	P
Vest4		0.47
MutPred		0.23		Gain of ubiquitination at E432 (P = 0.0016);
MVP		0.86
ClinPred		0.98	D
GERP RS		5.0
Varity_R		0.48
gMVP		0.95

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: chr6-3154141;