16-89932549-C-T

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.58-22C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0882 in 1,607,320 control chromosomes in the GnomAD database, including 13,351 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.18 (5057 hom., cov: 33)
  • Exomes 𝑓: 0.078 (8294 hom.)
• Consequence: TUBB3 NM_006086.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: -0.623

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=-0.81).
• BP6: Variant 16-89932549-C-T is Benign according to our data. Variant chr16-89932549-C-T is described in ClinVar as [Benign]. Clinvar id is 160192.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-89932549-C-T is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.466 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TUBB3	NM_006086.4	c.58-22C>T		intron_variant		ENST00000315491.12
TUBB3	NM_001197181.2	c.-159-22C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TUBB3	ENST00000315491.12	c.58-22C>T		intron_variant		1	NM_006086.4	P1

Frequencies

GnomAD3 genomes AF: 0.183 AC: 27880 AN: 152128 Hom.: 5038 Cov.: 33

Gnomad AFR AF: 0.471

Gnomad AMI AF: 0.0548

Gnomad AMR AF: 0.119

Gnomad ASJ AF: 0.0962

Gnomad EAS AF: 0.00519

Gnomad SAS AF: 0.129

Gnomad FIN AF: 0.0289

Gnomad MID AF: 0.293

Gnomad NFE AF: 0.0701

Gnomad OTH AF: 0.172

GnomAD3 exomes AF: 0.0979 AC: 24491 AN: 250192 Hom.: 2616 AF XY: 0.0942 AC XY: 12769 AN XY: 135552

Gnomad AFR exome AF: 0.477

Gnomad AMR exome AF: 0.0691

Gnomad ASJ exome AF: 0.0984

Gnomad EAS exome AF: 0.00125

Gnomad SAS exome AF: 0.124

Gnomad FIN exome AF: 0.0288

Gnomad NFE exome AF: 0.0741

Gnomad OTH exome AF: 0.0981

GnomAD4 exome AF: 0.0782 AC: 113777 AN: 1455076 Hom.: 8294 Cov.: 30 AF XY: 0.0791 AC XY: 57266 AN XY: 724326

Gnomad4 AFR exome AF: 0.487

Gnomad4 AMR exome AF: 0.0763

Gnomad4 ASJ exome AF: 0.0983

Gnomad4 EAS exome AF: 0.00804

Gnomad4 SAS exome AF: 0.125

Gnomad4 FIN exome AF: 0.0321

Gnomad4 NFE exome AF: 0.0644

Gnomad4 OTH exome AF: 0.103

GnomAD4 genome AF: 0.183 AC: 27930 AN: 152244 Hom.: 5057 Cov.: 33 AF XY: 0.177 AC XY: 13215 AN XY: 74452

Gnomad4 AFR AF: 0.471

Gnomad4 AMR AF: 0.118

Gnomad4 ASJ AF: 0.0962

Gnomad4 EAS AF: 0.00520

Gnomad4 SAS AF: 0.129

Gnomad4 FIN AF: 0.0289

Gnomad4 NFE AF: 0.0701

Gnomad4 OTH AF: 0.171

Alfa AF: 0.0812 Hom.: 558

Bravo AF: 0.201

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, no assertion criteria provided

clinical testing

Genetic Services Laboratory, University of Chicago

-

- -

not provided Benign:1

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	-0.81
Cadd	Benign	0.84
Dann	Benign	0.95
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs2302897; hg19: chr16-89998957;