16-89932336-C-G

Position:

• chr16-89932336-C-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_006086.4(TUBB3):​c.58-235C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.205 in 152,226 control chromosomes in the GnomAD database, including 5,822 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.20 (5822 hom., cov: 33)
• Consequence: TUBB3 NM_006086.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.676

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 16-89932336-C-G is Benign according to our data. Variant chr16-89932336-C-G is described in ClinVar as [Benign]. Clinvar id is 1249821.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.492 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TUBB3	NM_006086.4	c.58-235C>G		intron_variant		ENST00000315491.12	NP_006077.2
TUBB3	NM_001197181.2	c.-159-235C>G		intron_variant			NP_001184110.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TUBB3	ENST00000315491.12	c.58-235C>G		intron_variant		1	NM_006086.4	ENSP00000320295	P1

Frequencies

GnomAD3 genomes AF: 0.205 AC: 31146 AN: 152108 Hom.: 5799 Cov.: 33

Gnomad AFR AF: 0.497

Gnomad AMI AF: 0.0559

Gnomad AMR AF: 0.137

Gnomad ASJ AF: 0.125

Gnomad EAS AF: 0.00712

Gnomad SAS AF: 0.210

Gnomad FIN AF: 0.0371

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.0888

Gnomad OTH AF: 0.196

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

GnomAD4 genome AF: 0.205 AC: 31206 AN: 152226 Hom.: 5822 Cov.: 33 AF XY: 0.199 AC XY: 14797 AN XY: 74438

Gnomad4 AFR AF: 0.497

Gnomad4 AMR AF: 0.137

Gnomad4 ASJ AF: 0.125

Gnomad4 EAS AF: 0.00713

Gnomad4 SAS AF: 0.210

Gnomad4 FIN AF: 0.0371

Gnomad4 NFE AF: 0.0887

Gnomad4 OTH AF: 0.196

Alfa AF: 0.153 Hom.: 464

Bravo AF: 0.221

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 26, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.5
DANN	Benign	0.64

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: rs28521461; hg19: chr16-89998744;