12-49274138-T-C

Variant names:

• chr12-49274138-T-C
• rs10875941
• NM_032704.5:c.*911T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032704.5(TUBA1C):​c.*911T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.389 in 151,724 control chromosomes in the GnomAD database, including 13,784 homozygotes. 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 0.39 (13780 hom., cov: 30)
  • Exomes 𝑓: 0.37 (4 hom.)
• Consequence: TUBA1C NM_032704.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.576
• Publications: 5 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.738 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TUBA1C	NM_032704.5	MANE Select	c.*911T>C		3_prime_UTR	Exon 4 of 4	NP_116093.1
	TUBA1C	NM_001303115.2		c.*911T>C		3_prime_UTR	Exon 6 of 6	NP_001290044.1
	TUBA1C	NM_001303116.2		c.*911T>C		3_prime_UTR	Exon 5 of 5	NP_001290045.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TUBA1C	ENST00000301072.11	TSL:1 MANE Select	c.*911T>C		3_prime_UTR	Exon 4 of 4	ENSP00000301072.7

Frequencies

GnomAD3 genomes AF: 0.389 AC: 58926 AN: 151568 Hom.: 13756 Cov.: 30

Gnomad AFR AF: 0.620

Gnomad AMI AF: 0.251

Gnomad AMR AF: 0.307

Gnomad ASJ AF: 0.260

Gnomad EAS AF: 0.758

Gnomad SAS AF: 0.571

Gnomad FIN AF: 0.239

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.259

Gnomad OTH AF: 0.354

GnomAD4 exome AF: 0.368 AC: 14 AN: 38 Hom.: 4 Cov.: 0 AF XY: 0.333 AC XY: 10 AN XY: 30

African (AFR) AF: 1.00 AC: 2 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 1.00 AC: 2 AN: 2

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.294 AC: 10 AN: 34

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.389 AC: 58995 AN: 151686 Hom.: 13780 Cov.: 30 AF XY: 0.392 AC XY: 29083 AN XY: 74128

African (AFR) AF: 0.620 AC: 25620 AN: 41308

American (AMR) AF: 0.307 AC: 4675 AN: 15224

Ashkenazi Jewish (ASJ) AF: 0.260 AC: 901 AN: 3470

East Asian (EAS) AF: 0.758 AC: 3917 AN: 5166

South Asian (SAS) AF: 0.571 AC: 2733 AN: 4790

European-Finnish (FIN) AF: 0.239 AC: 2515 AN: 10522

Middle Eastern (MID) AF: 0.337 AC: 99 AN: 294

European-Non Finnish (NFE) AF: 0.259 AC: 17552 AN: 67898

Other (OTH) AF: 0.359 AC: 754 AN: 2102

Alfa AF: 0.289 Hom.: 13889

Bravo AF: 0.398

Asia WGS AF: 0.651 AC: 2263 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.8
DANN	Benign	0.38
PhyloP100		0.58

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: rs10875941; hg19: chr12-49667921;