10-5393539-T-A

Variant names:

• chr10-5393539-T-A
• NM_024803.3:c.1319A>T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_024803.3(TUBAL3):​c.1319A>T​(p.Glu440Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TUBAL3 NM_024803.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.07

Genes affected

TUBAL3 (HGNC:23534): (tubulin alpha like 3) Predicted to enable GTP binding activity. Predicted to be a structural constituent of cytoskeleton. Predicted to be involved in microtubule cytoskeleton organization and mitotic cell cycle. Predicted to be active in cytoplasm and microtubule. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TUBAL3	NM_024803.3	c.1319A>T	p.Glu440Val	missense_variant	Exon 4 of 4	ENST00000380419.8	NP_079079.1
TUBAL3	NM_001171864.2	c.1199A>T	p.Glu400Val	missense_variant	Exon 4 of 4		NP_001165335.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TUBAL3	ENST00000380419.8	c.1319A>T	p.Glu440Val	missense_variant	Exon 4 of 4	1	NM_024803.3	ENSP00000369784.3
TUBAL3	ENST00000479328.1	c.1199A>T	p.Glu400Val	missense_variant	Exon 4 of 4	1		ENSP00000418799.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 03, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1319A>T (p.E440V) alteration is located in exon 4 (coding exon 4) of the TUBAL3 gene. This alteration results from a A to T substitution at nucleotide position 1319, causing the glutamic acid (E) at amino acid position 440 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.0
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.31	T;.
Eigen	Benign	0.059
Eigen_PC	Benign	-0.035
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.96	D;D
M_CAP	Benign	0.030	D
MetaRNN	Uncertain	0.67	D;D
MetaSVM	Uncertain	0.36	D
MutationAssessor	Pathogenic	3.1	M;.
PrimateAI	Benign	0.35	T
PROVEAN	Uncertain	-4.3	D;D
REVEL	Uncertain	0.48
Sift	Pathogenic	0.0	D;D
Sift4G	Uncertain	0.024	D;D
Polyphen		0.59	P;P
Vest4		0.60
MutPred		0.43		Loss of disorder (P = 0.0019);.;
MVP		0.87
MPC		0.24
ClinPred		0.97	D
GERP RS		3.1
Varity_R		0.40
gMVP		0.32

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: chr10-5435502;