chr10-5393974-A-T

Position:

• chr10-5393974-A-T

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The ENST00000380419.8(TUBAL3):​c.884T>A​(p.Val295Glu) 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 pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TUBAL3 ENST00000380419.8 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.07

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 Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.982

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TUBAL3	NM_024803.3	c.884T>A	p.Val295Glu	missense_variant	4/4	ENST00000380419.8	NP_079079.1
TUBAL3	NM_001171864.2	c.764T>A	p.Val255Glu	missense_variant	4/4		NP_001165335.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TUBAL3	ENST00000380419.8	c.884T>A	p.Val295Glu	missense_variant	4/4	1	NM_024803.3	ENSP00000369784.3
TUBAL3	ENST00000479328.1	c.764T>A	p.Val255Glu	missense_variant	4/4	1		ENSP00000418799.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 81

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 23, 2024

The c.884T>A (p.V295E) alteration is located in exon 4 (coding exon 4) of the TUBAL3 gene. This alteration results from a T to A substitution at nucleotide position 884, causing the valine (V) at amino acid position 295 to be replaced by a glutamic acid (E). 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	Pathogenic	0.65
BayesDel_addAF	Pathogenic	0.46	D
BayesDel_noAF	Pathogenic	0.42
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.79	D;.
Eigen	Pathogenic	0.76
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.86	D;D
M_CAP	Benign	0.047	D
MetaRNN	Pathogenic	0.98	D;D
MetaSVM	Pathogenic	1.0	D
MutationAssessor	Pathogenic	4.7	H;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Benign	0.46	T
PROVEAN	Pathogenic	-4.8	D;D
REVEL	Pathogenic	0.74
Sift	Pathogenic	0.0	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		1.0	D;D
Vest4		0.95
MutPred		0.82		Gain of disorder (P = 0.0014);.;
MVP		0.96
MPC		0.51
ClinPred		1.0	D
GERP RS		4.2
Varity_R		0.81
gMVP		0.80

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: chr10-5435937;