12-49273036-G-A

Position:

• chr12-49273036-G-A

Variant summary

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

The NM_032704.5(TUBA1C):​c.1159G>A​(p.Ala387Thr) variant causes a missense change involving the alteration of a conserved nucleotide. 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: TUBA1C NM_032704.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.57

Genes affected

TUBA1C (HGNC:20768): (tubulin alpha 1c) 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. Located in microtubule cytoskeleton and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

(HGNC:):

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/exons	MANE	UniProt
TUBA1C	NM_032704.5	c.1159G>A	p.Ala387Thr	missense_variant	4/4	ENST00000301072.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TUBA1C	ENST00000301072.11	c.1159G>A	p.Ala387Thr	missense_variant	4/4	1	NM_032704.5	P1
	ENST00000550468.2	n.271C>T		non_coding_transcript_exon_variant	1/2	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 36

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

Nov 18, 2022

The c.1159G>A (p.A387T) alteration is located in exon 4 (coding exon 4) of the TUBA1C gene. This alteration results from a G to A substitution at nucleotide position 1159, causing the alanine (A) at amino acid position 387 to be replaced by a threonine (T). 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	0.76
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.070
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.39	T;T;.
Eigen	Uncertain	0.59
Eigen_PC	Uncertain	0.54
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.97	D;D;D
M_CAP	Uncertain	0.29	D
MetaRNN	Uncertain	0.73	D;D;D
MetaSVM	Uncertain	0.42	D
MutationAssessor	Uncertain	2.8	.;M;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-2.1	N;N;.
REVEL	Pathogenic	0.67
Sift	Pathogenic	0.0	D;D;.
Sift4G	Uncertain	0.042	D;T;.
Polyphen		1.0	D;D;.
Vest4		0.68
MutPred		0.51		Gain of catalytic residue at W458 (P = 6e-04);.;.;
MVP		0.80
MPC		2.7
ClinPred		0.99	D
GERP RS		4.0
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		3.7
Varity_R		0.49
gMVP		0.72

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: chr12-49666819;