chr12-49272511-A-G

Variant names:

• chr12-49272511-A-G
• rs376776166
• NM_032704.5:c.634A>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_032704.5(TUBA1C):​c.634A>G​(p.Ile212Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,609,456 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 30)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: TUBA1C NM_032704.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.87

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.41008806).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TUBA1C	NM_032704.5	c.634A>G	p.Ile212Val	missense_variant	Exon 4 of 4	ENST00000301072.11	NP_116093.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TUBA1C	ENST00000301072.11	c.634A>G	p.Ile212Val	missense_variant	Exon 4 of 4	1	NM_032704.5	ENSP00000301072.7

Frequencies

GnomAD3 genomes AF: 0.00000660 AC: 1 AN: 151514 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1457942 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 724812

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00000660 AC: 1 AN: 151514 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 73954

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Uncertain	0.097	D
BayesDel_noAF	Benign	-0.10
CADD	Benign	23
DANN	Benign	0.93
DEOGEN2	Benign	0.076	T;T
Eigen	Benign	0.16
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.91	D;D
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.41	T;T
MetaSVM	Benign	-0.37	T
MutationAssessor	Pathogenic	3.0	.;M
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-0.62	N;N
REVEL	Uncertain	0.47
Sift	Benign	0.030	D;D
Sift4G	Benign	0.062	T;T
Polyphen		0.030	B;B
Vest4		0.60
MutPred		0.63		Gain of catalytic residue at I279 (P = 0.0041);.;
MVP		0.82
MPC		1.3
ClinPred		0.92	D
GERP RS		3.4
Varity_R		0.082
gMVP		0.86

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: rs376776166; hg19: chr12-49666294;