chr12-49269589-G-A

Variant names:

• chr12-49269589-G-A
• rs139215369
• NM_032704.5:c.128G>A

Variant summary

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

The NM_032704.5(TUBA1C):​c.128G>A​(p.Gly43Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,892 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: TUBA1C NM_032704.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.02

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]

ENSG00000258232 (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 rank	MANE	Protein	UniProt
TUBA1C	NM_032704.5	c.128G>A	p.Gly43Glu	missense_variant	Exon 2 of 4	ENST00000301072.11	NP_116093.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TUBA1C	ENST00000301072.11	c.128G>A	p.Gly43Glu	missense_variant	Exon 2 of 4	1	NM_032704.5	ENSP00000301072.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251496 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135922

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461892 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727246

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000224

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.84
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	0.050
CADD	Pathogenic	26
DANN	Benign	0.95
DEOGEN2	Benign	0.026	T;T;.;.
Eigen	Uncertain	0.19
Eigen_PC	Benign	0.22
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.81	T;T;T;T
M_CAP	Benign	0.063	D
MetaRNN	Uncertain	0.61	D;D;D;D
MetaSVM	Benign	-0.35	T
MutationAssessor	Benign	1.4	.;L;.;.
PrimateAI	Pathogenic	0.85	D
PROVEAN	Uncertain	-2.7	D;D;D;.
REVEL	Uncertain	0.47
Sift	Pathogenic	0.0	D;D;.;.
Sift4G	Benign	0.14	T;T;T;.
Polyphen		0.0020	B;P;.;.
Vest4		0.67
MutPred		0.39		Gain of catalytic residue at D117 (P = 0.0424);.;.;.;
MVP		0.78
MPC		1.7
ClinPred		0.96	D
GERP RS		2.6
Varity_R		0.67
gMVP		0.69

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

LitVar

Other links and lift over

dbSNP: rs139215369; hg19: chr12-49663372; COSMIC: COSV56509420; COSMIC: COSV56509420;