rs2335451

chr12-49271003-C-Achr12-49271003-C-Gchr12-49271003-C-T

Variant summary

Our verdict is Benign. Variant got -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

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TUBA1C	NM_032704.5	c.375+1027C>A		intron_variant		ENST00000301072.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TUBA1C	ENST00000301072.11	c.375+1027C>A		intron_variant		1	NM_032704.5	P1
	ENST00000550468.2	n.637+1667G>T		intron_variant, non_coding_transcript_variant		5

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

Gnomad4 AFR AF: 0.616

Gnomad4 AMR AF: 0.296

Gnomad4 ASJ AF: 0.232

Gnomad4 EAS AF: 0.762

Gnomad4 SAS AF: 0.542

Gnomad4 FIN AF: 0.226

Gnomad4 NFE AF: 0.242

Gnomad4 OTH AF: 0.344

Alfa AF: 0.270 Hom.: 10119

Bravo AF: 0.396

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.40
Dann	Benign	0.55

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: rs2335451; hg19: chr12-49664786;