Genetic Variant TUBA1C:p.Leu217Ile (chr12-49272526-C-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_032704.5(TUBA1C):c.649C>A(p.Leu217Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000823 in 1,457,618 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 30)

Exomes 𝑓: 0.0000082 ( 0 hom. )

Consequence

TUBA1C
NM_032704.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.81

Publications

0 publications found

Variant links:

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]

TUBA1C links:

ENSG00000258232 (HGNC:):

ENSG00000258232 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2

High AC in GnomAdExome4 at 12 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032704.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TUBA1C	NM_032704.5	MANE Select	c.649C>A	p.Leu217Ile	missense	Exon 4 of 4	NP_116093.1	Q9BQE3
TUBA1C	NM_001303114.1		c.859C>A	p.Leu287Ile	missense	Exon 4 of 4	NP_001290043.1	F5H5D3
TUBA1C	NM_001303115.2		c.544C>A	p.Leu182Ile	missense	Exon 6 of 6	NP_001290044.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TUBA1C	ENST00000301072.11	TSL:1 MANE Select	c.649C>A	p.Leu217Ile	missense	Exon 4 of 4	ENSP00000301072.7	Q9BQE3
TUBA1C	ENST00000541364.5	TSL:2	c.859C>A	p.Leu287Ile	missense	Exon 4 of 4	ENSP00000443475.1	F5H5D3
TUBA1C	ENST00000931110.1		c.643C>A	p.Leu215Ile	missense	Exon 4 of 4	ENSP00000601169.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000812

AC:

AN:

246210

AF XY:

0.0000149

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000111

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000823

AC:

AN:

1457618

Hom.:

Cov.:

AF XY:

0.00000690

AC XY:

AN XY:

724550

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33306

American (AMR)

AF:

0.00

AC:

AN:

44652

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26108

East Asian (EAS)

AF:

0.000303

AC:

AN:

39622

South Asian (SAS)

AF:

0.00

AC:

AN:

86160

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53378

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4414

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1109854

Other (OTH)

AF:

0.00

AC:

AN:

60124

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ExAC

AF:

0.0000165

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.76

BayesDel_addAF

Uncertain

0.092

BayesDel_noAF

Benign

-0.11

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.13

Eigen

Pathogenic

0.70

Eigen_PC

Uncertain

0.66

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.95

M_CAP

Uncertain

0.10

MetaRNN

Uncertain

0.57

MetaSVM

Uncertain

0.63

MutationAssessor

Pathogenic

3.9

PhyloP100

5.8

PrimateAI

Uncertain

0.73

PROVEAN

Benign

-1.4

REVEL

Uncertain

0.63

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.0060

Polyphen

0.051

Vest4

0.63

MutPred

0.73

Gain of catalytic residue at R291 (P = 0.0156)

MVP

0.77

MPC

2.0

ClinPred

0.97

GERP RS

4.6

Varity_R

0.35

gMVP

0.83

Mutation Taster

=64/36

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over