rs2335451

Variant names:

• chr12-49271003-C-A
• rs2335451
• NM_032704.5:c.375+1027C>A

Your query was ambiguous. Multiple possible variants found:

• chr12-49271003-C-A
• chr12-49271003-C-G
• chr12-49271003-C-T

Variant summary

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

The NM_032704.5(TUBA1C):​c.375+1027C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.379 in 148,170 control chromosomes in the GnomAD database, including 12,867 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 0.38 (12867 hom., cov: 31)
• Consequence: TUBA1C NM_032704.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.15
• Publications: 6 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: 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 = 0.742 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.375+1027C>A		intron	N/A	NP_116093.1
	TUBA1C	NM_001303114.1		c.585+1027C>A		intron	N/A	NP_001290043.1
	TUBA1C	NM_001303115.2		c.270+1027C>A		intron	N/A	NP_001290044.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TUBA1C	ENST00000301072.11	TSL:1 MANE Select	c.375+1027C>A		intron	N/A	ENSP00000301072.7
	TUBA1C	ENST00000541364.5	TSL:2	c.585+1027C>A		intron	N/A	ENSP00000443475.1
	TUBA1C	ENST00000548470.1	TSL:2	n.191+1027C>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.379 AC: 56107 AN: 148046 Hom.: 12844 Cov.: 31

Gnomad AFR AF: 0.616

Gnomad AMI AF: 0.215

Gnomad AMR AF: 0.297

Gnomad ASJ AF: 0.232

Gnomad EAS AF: 0.762

Gnomad SAS AF: 0.543

Gnomad FIN AF: 0.226

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.242

Gnomad OTH AF: 0.339

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.379 AC: 56180 AN: 148170 Hom.: 12867 Cov.: 31 AF XY: 0.382 AC XY: 27723 AN XY: 72518

African (AFR) AF: 0.616 AC: 25444 AN: 41284

American (AMR) AF: 0.296 AC: 4441 AN: 14986

Ashkenazi Jewish (ASJ) AF: 0.232 AC: 743 AN: 3202

East Asian (EAS) AF: 0.762 AC: 3934 AN: 5162

South Asian (SAS) AF: 0.542 AC: 2484 AN: 4580

European-Finnish (FIN) AF: 0.226 AC: 2334 AN: 10306

Middle Eastern (MID) AF: 0.296 AC: 81 AN: 274

European-Non Finnish (NFE) AF: 0.242 AC: 15836 AN: 65488

Other (OTH) AF: 0.344 AC: 697 AN: 2024

Alfa AF: 0.298 Hom.: 28491

Bravo AF: 0.396

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.40
DANN	Benign	0.55
PhyloP100		-2.1
Mutation Taster		=100/0	polymorphism (auto)

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: rs2335451; hg19: chr12-49664786;