12-49128628-C-T

Position:

• chr12-49128628-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_006082.3(TUBA1B):​c.686G>A​(p.Arg229His) 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: 31)
• Consequence: TUBA1B NM_006082.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.50

Genes affected

TUBA1B (HGNC:18809): (tubulin alpha 1b) Enables double-stranded RNA binding activity and ubiquitin protein ligase binding activity. Predicted to be involved in microtubule cytoskeleton organization and mitotic cell cycle. Predicted to act upstream of or within cellular response to interleukin-4. Located in microtubule. [provided by Alliance of Genome Resources, Apr 2022]

TUBA1B (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.915

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TUBA1B	NM_006082.3	c.686G>A	p.Arg229His	missense_variant	4/4	ENST00000336023.9	NP_006073.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TUBA1B	ENST00000336023.9	c.686G>A	p.Arg229His	missense_variant	4/4	1	NM_006082.3	ENSP00000336799.5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

TUBA1B-associated neurodevelopmental disorder Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Institute of Human Genetics, University of Leipzig Medical Center

Apr 13, 2023

Criteria applied: PS2_MOD,PM2_SUP,PP2,PP3 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.90
BayesDel_addAF	Uncertain	0.057	T
BayesDel_noAF	Benign	-0.16
CADD	Benign	21
DANN	Benign	0.95
DEOGEN2	Uncertain	0.45	T;.
Eigen	Uncertain	0.38
Eigen_PC	Uncertain	0.37
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.89	D;T
M_CAP	Uncertain	0.17	D
MetaRNN	Pathogenic	0.92	D;D
MetaSVM	Benign	-0.34	T
MutationAssessor	Benign	1.5	L;.
PrimateAI	Uncertain	0.71	T
PROVEAN	Uncertain	-3.2	D;D
REVEL	Uncertain	0.57
Sift4G	Benign	0.082	T;.
Polyphen		1.0	D;.
Vest4		0.53
MutPred		0.78		Loss of MoRF binding (P = 0.0768);.;
MVP		0.99
MPC		4.1
ClinPred		0.93	D
GERP RS		4.2
Varity_R		0.86
gMVP		0.96

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: chr12-49522411;