10-5393807-C-T

Variant names:

• chr10-5393807-C-T
• NM_024803.3:c.1051G>A

Variant summary

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

The NM_024803.3(TUBAL3):​c.1051G>A​(p.Val351Ile) 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: 4.91

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.1051G>A	p.Val351Ile	missense_variant	Exon 4 of 4	ENST00000380419.8	NP_079079.1
TUBAL3	NM_001171864.2	c.931G>A	p.Val311Ile	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.1051G>A	p.Val351Ile	missense_variant	Exon 4 of 4	1	NM_024803.3	ENSP00000369784.3
TUBAL3	ENST00000479328.1	c.931G>A	p.Val311Ile	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

Jul 14, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1051G>A (p.V351I) alteration is located in exon 4 (coding exon 4) of the TUBAL3 gene. This alteration results from a G to A substitution at nucleotide position 1051, causing the valine (V) at amino acid position 351 to be replaced by an isoleucine (I). 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	0.19
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.030
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.30	T;.
Eigen	Uncertain	0.63
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.96	D;D
M_CAP	Benign	0.016	T
MetaRNN	Uncertain	0.63	D;D
MetaSVM	Pathogenic	0.96	D
MutationAssessor	Pathogenic	4.0	H;.
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-0.80	N;N
REVEL	Uncertain	0.58
Sift	Pathogenic	0.0	D;D
Sift4G	Uncertain	0.0060	D;D
Polyphen		0.70	P;D
Vest4		0.27
MutPred		0.75		Loss of sheet (P = 0.0817);.;
MVP		0.80
MPC		0.063
ClinPred		1.0	D
GERP RS		4.4
Varity_R		0.37
gMVP		0.33

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: chr10-5435770;