16-89932386-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_006086.4(TUBB3):c.58-185G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.329 in 152,052 control chromosomes in the GnomAD database, including 8,784 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.33 (8784 hom., cov: 32)
• Consequence: TUBB3 NM_006086.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.804

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 16-89932386-G-A is Benign according to our data. Variant chr16-89932386-G-A is described in ClinVar as [Benign]. Clinvar id is 670258.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.609 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TUBB3	NM_006086.4	c.58-185G>A		intron_variant		ENST00000315491.12
TUBB3	NM_001197181.2	c.-159-185G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TUBB3	ENST00000315491.12	c.58-185G>A		intron_variant		1	NM_006086.4	P1

Frequencies

GnomAD3 genomes AF: 0.329 AC: 50051 AN: 151934 Hom.: 8769 Cov.: 32

Gnomad AFR AF: 0.301

Gnomad AMI AF: 0.254

Gnomad AMR AF: 0.419

Gnomad ASJ AF: 0.230

Gnomad EAS AF: 0.628

Gnomad SAS AF: 0.451

Gnomad FIN AF: 0.429

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.286

Gnomad OTH AF: 0.312

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

GnomAD4 genome AF: 0.329 AC: 50097 AN: 152052 Hom.: 8784 Cov.: 32 AF XY: 0.341 AC XY: 25327 AN XY: 74310

Gnomad4 AFR AF: 0.302

Gnomad4 AMR AF: 0.420

Gnomad4 ASJ AF: 0.230

Gnomad4 EAS AF: 0.627

Gnomad4 SAS AF: 0.449

Gnomad4 FIN AF: 0.429

Gnomad4 NFE AF: 0.286

Gnomad4 OTH AF: 0.313

Alfa AF: 0.300 Hom.: 11722

Bravo AF: 0.328

Asia WGS AF: 0.492 AC: 1715 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

Jun 14, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	5.1
Dann	Benign	0.78

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs2302898; hg19: chr16-89998794;