16-89932240-T-G

Position:

• chr16-89932240-T-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.58-331T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0578 in 415,250 control chromosomes in the GnomAD database, including 2,812 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.099 (2137 hom., cov: 33)
  • Exomes 𝑓: 0.034 (675 hom.)
• Consequence: TUBB3 NM_006086.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.267

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=-0.83).
• BP6: Variant 16-89932240-T-G is Benign according to our data. Variant chr16-89932240-T-G is described in ClinVar as [Benign]. Clinvar id is 1277879.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.308 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TUBB3	NM_006086.4	c.58-331T>G		intron_variant		ENST00000315491.12	NP_006077.2
TUBB3	NM_001197181.2	c.-159-331T>G		intron_variant			NP_001184110.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TUBB3	ENST00000315491.12	c.58-331T>G		intron_variant		1	NM_006086.4	ENSP00000320295	P1

Frequencies

GnomAD3 genomes AF: 0.0984 AC: 14975 AN: 152132 Hom.: 2121 Cov.: 33

Gnomad AFR AF: 0.312

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.0404

Gnomad ASJ AF: 0.0230

Gnomad EAS AF: 0.00462

Gnomad SAS AF: 0.112

Gnomad FIN AF: 0.00264

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.00885

Gnomad OTH AF: 0.0718

GnomAD4 exome AF: 0.0342 AC: 8993 AN: 263000 Hom.: 675 AF XY: 0.0393 AC XY: 5506 AN XY: 140002

Gnomad4 AFR exome AF: 0.318

Gnomad4 AMR exome AF: 0.0265

Gnomad4 ASJ exome AF: 0.0195

Gnomad4 EAS exome AF: 0.00596

Gnomad4 SAS exome AF: 0.101

Gnomad4 FIN exome AF: 0.00416

Gnomad4 NFE exome AF: 0.00822

Gnomad4 OTH exome AF: 0.0347

GnomAD4 genome AF: 0.0987 AC: 15025 AN: 152250 Hom.: 2137 Cov.: 33 AF XY: 0.0967 AC XY: 7199 AN XY: 74466

Gnomad4 AFR AF: 0.312

Gnomad4 AMR AF: 0.0403

Gnomad4 ASJ AF: 0.0230

Gnomad4 EAS AF: 0.00463

Gnomad4 SAS AF: 0.112

Gnomad4 FIN AF: 0.00264

Gnomad4 NFE AF: 0.00885

Gnomad4 OTH AF: 0.0720

Alfa AF: 0.0148 Hom.: 31

Bravo AF: 0.108

Asia WGS AF: 0.0740 AC: 256 AN: 3478

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	-0.83
CADD	Benign	10
DANN	Benign	0.75

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: rs58336812; hg19: chr16-89998648;