NM_032704.5:c.349C>T

Variant names:

• chr12-49269950-C-T
• rs752527294
• NM_032704.5:c.349C>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4 BS2

The NM_032704.5(TUBA1C):​c.349C>T​(p.Leu117Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,884 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: TUBA1C NM_032704.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.20
• Publications: 1 publications found

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

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2713355).
• BS2: High AC in GnomAdExome4 at 5 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TUBA1C	NM_032704.5	MANE Select	c.349C>T	p.Leu117Phe	missense	Exon 3 of 4	NP_116093.1	Q9BQE3
	TUBA1C	NM_001303114.1		c.559C>T	p.Leu187Phe	missense	Exon 3 of 4	NP_001290043.1	F5H5D3
	TUBA1C	NM_001303115.2		c.244C>T	p.Leu82Phe	missense	Exon 5 of 6	NP_001290044.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TUBA1C	ENST00000301072.11	TSL:1 MANE Select	c.349C>T	p.Leu117Phe	missense	Exon 3 of 4	ENSP00000301072.7	Q9BQE3
	TUBA1C	ENST00000541364.5	TSL:2	c.559C>T	p.Leu187Phe	missense	Exon 3 of 4	ENSP00000443475.1	F5H5D3
	TUBA1C	ENST00000931110.1		c.343C>T	p.Leu115Phe	missense	Exon 3 of 4	ENSP00000601169.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000159 AC: 4 AN: 251494 AF XY: 0.0000221

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000163

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000879

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461884 Hom.: 0 Cov.: 31 AF XY: 0.00000550 AC XY: 4 AN XY: 727242

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.000126 AC: 5 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112012

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.15
CADD	Uncertain	24
DANN	Benign	0.97
DEOGEN2	Benign	0.040	T
Eigen	Benign	0.12
Eigen_PC	Benign	0.12
FATHMM_MKL	Benign	0.71	D
LIST_S2	Benign	0.54	T
M_CAP	Benign	0.083	D
MetaRNN	Benign	0.27	T
MetaSVM	Uncertain	-0.0028	T
MutationAssessor	Pathogenic	3.4	M
PhyloP100		1.2
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-1.9	N
REVEL	Uncertain	0.34
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.035	D
Polyphen		0.54	P
Vest4		0.54
MutPred		0.38		Gain of catalytic residue at L189 (P = 0.0084)
MVP		0.75
MPC		0.69
ClinPred		0.76	D
GERP RS		4.0
Varity_R		0.15
gMVP		0.62
Mutation Taster		=39/61	disease causing

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: rs752527294; hg19: chr12-49663733;