NM_006082.3:c.492G>C

Variant names:

• chr12-49128822-C-G
• rs1057548
• NM_006082.3:c.492G>C

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_006082.3(TUBA1B):​c.492G>C​(p.Lys164Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. K164K) has been classified as Benign.

• Frequency: Genomes: not found (cov: 30)
• Consequence: TUBA1B NM_006082.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.61
• Publications: 20 publications found

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-AS1 (HGNC:56356): (TUBA1B antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.829

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006082.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TUBA1B	NM_006082.3	MANE Select	c.492G>C	p.Lys164Asn	missense	Exon 4 of 4	NP_006073.2	P68363-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TUBA1B	ENST00000336023.9	TSL:1 MANE Select	c.492G>C	p.Lys164Asn	missense	Exon 4 of 4	ENSP00000336799.5	P68363-1
	TUBA1B	ENST00000332858.10	TSL:1	n.2162G>C		non_coding_transcript_exon	Exon 3 of 3
	TUBA1B	ENST00000920098.1		c.435G>C	p.Lys145Asn	missense	Exon 4 of 4	ENSP00000590157.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 88

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Uncertain	0.035	T
BayesDel_noAF	Benign	-0.19
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.53	D
Eigen	Pathogenic	0.73
Eigen_PC	Uncertain	0.61
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Pathogenic	0.30	D
MetaRNN	Pathogenic	0.83	D
MetaSVM	Uncertain	0.50	D
MutationAssessor	Pathogenic	4.1	H
PhyloP100		2.6
PrimateAI	Pathogenic	0.83	D
PROVEAN	Uncertain	-3.5	D
REVEL	Pathogenic	0.72
Sift4G	Uncertain	0.015	D
Polyphen		0.99	D
Vest4		0.65
MutPred		0.71		Loss of methylation at K164 (P = 0.0149)
MVP		0.98
MPC		4.0
ClinPred		1.0	D
GERP RS		4.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.94
gMVP		0.99
Mutation Taster		=54/46	polymorphism

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

Other links and lift over

dbSNP: rs1057548; hg19: chr12-49522605;