16-89932544-A-AC

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_006086.4(TUBB3):c.58-20dup variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0216 in 1,596,432 control chromosomes in the GnomAD database, including 655 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.021 (49 hom., cov: 33)
  • Exomes 𝑓: 0.022 (606 hom.)
• Consequence: TUBB3 NM_006086.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.186

Genes affected

TUBB3 (HGNC:20772): (tubulin beta 3 class III) This gene encodes a class III member of the beta tubulin protein family. Beta tubulins are one of two core protein families (alpha and beta tubulins) that heterodimerize and assemble to form microtubules. This protein is primarily expressed in neurons and may be involved in neurogenesis and axon guidance and maintenance. Mutations in this gene are the cause of congenital fibrosis of the extraocular muscles type 3. Alternate splicing results in multiple transcript variants. A pseudogene of this gene is found on chromosome 6. [provided by RefSeq, Oct 2010]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 16-89932544-A-AC is Benign according to our data. Variant chr16-89932544-A-AC is described in ClinVar as [Benign]. Clinvar id is 1175481.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0793 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TUBB3	NM_006086.4	c.58-20dup		intron_variant		ENST00000315491.12
TUBB3	NM_001197181.2	c.-159-20dup		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TUBB3	ENST00000315491.12	c.58-20dup		intron_variant		1	NM_006086.4	P1

Frequencies

GnomAD3 genomes AF: 0.0209 AC: 3134 AN: 150300 Hom.: 47 Cov.: 33

Gnomad AFR AF: 0.0216

Gnomad AMI AF: 0.00991

Gnomad AMR AF: 0.0182

Gnomad ASJ AF: 0.0286

Gnomad EAS AF: 0.00255

Gnomad SAS AF: 0.0860

Gnomad FIN AF: 0.00842

Gnomad MID AF: 0.0160

Gnomad NFE AF: 0.0194

Gnomad OTH AF: 0.0233

GnomAD3 exomes AF: 0.0239 AC: 5966 AN: 249880 Hom.: 145 AF XY: 0.0269 AC XY: 3642 AN XY: 135426

Gnomad AFR exome AF: 0.0214

Gnomad AMR exome AF: 0.0120

Gnomad ASJ exome AF: 0.0285

Gnomad EAS exome AF: 0.00218

Gnomad SAS exome AF: 0.0830

Gnomad FIN exome AF: 0.0101

Gnomad NFE exome AF: 0.0176

Gnomad OTH exome AF: 0.0239

GnomAD4 exome AF: 0.0217 AC: 31333 AN: 1446020 Hom.: 606 Cov.: 28 AF XY: 0.0234 AC XY: 16858 AN XY: 720354

Gnomad4 AFR exome AF: 0.0209

Gnomad4 AMR exome AF: 0.0128

Gnomad4 ASJ exome AF: 0.0265

Gnomad4 EAS exome AF: 0.00134

Gnomad4 SAS exome AF: 0.0795

Gnomad4 FIN exome AF: 0.0105

Gnomad4 NFE exome AF: 0.0184

Gnomad4 OTH exome AF: 0.0252

GnomAD4 genome AF: 0.0209 AC: 3144 AN: 150412 Hom.: 49 Cov.: 33 AF XY: 0.0207 AC XY: 1521 AN XY: 73354

Gnomad4 AFR AF: 0.0217

Gnomad4 AMR AF: 0.0184

Gnomad4 ASJ AF: 0.0286

Gnomad4 EAS AF: 0.00255

Gnomad4 SAS AF: 0.0862

Gnomad4 FIN AF: 0.00842

Gnomad4 NFE AF: 0.0194

Gnomad4 OTH AF: 0.0250

Asia WGS AF: 0.0480 AC: 167 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 14, 2020

- -

Computational scores

Source: dbNSFP v4.3

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: rs112388869; hg19: chr16-89998952;