16-89923273-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS1

The NM_001197181.2(TUBB3):c.-160+1028C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000901 in 675,846 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0032 (1 hom., cov: 33)
  • Exomes 𝑓: 0.00025 (1 hom.)
• Consequence: TUBB3 NM_001197181.2 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.318

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.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant 16-89923273-C-T is Benign according to our data. Variant chr16-89923273-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1188692.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00317 (479/151238) while in subpopulation AFR AF= 0.0111 (458/41442). AF 95% confidence interval is 0.0102. There are 1 homozygotes in gnomad4. There are 231 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TUBB3	NM_001197181.2	c.-160+1028C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TUBB3	ENST00000554444.5	c.-160+1028C>T		intron_variant		2
TUBB3	ENST00000555810.5	c.-160+1842C>T		intron_variant		3
TUBB3	ENST00000556565.5	c.-160+1090C>T		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.00316 AC: 477 AN: 151130 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.0110

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000858

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000443

Gnomad OTH AF: 0.00241

GnomAD4 exome AF: 0.000248 AC: 130 AN: 524608 Hom.: 1 Cov.: 8 AF XY: 0.000206 AC XY: 54 AN XY: 262118

Gnomad4 AFR exome AF: 0.0106

Gnomad4 AMR exome AF: 0.000358

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000946

Gnomad4 OTH exome AF: 0.000618

GnomAD4 genome AF: 0.00317 AC: 479 AN: 151238 Hom.: 1 Cov.: 33 AF XY: 0.00313 AC XY: 231 AN XY: 73892

Gnomad4 AFR AF: 0.0111

Gnomad4 AMR AF: 0.000857

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000443

Gnomad4 OTH AF: 0.00239

Alfa AF: 0.00243 Hom.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 16, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
Cadd	Benign	11
Dann	Benign	0.83

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: rs558683187; hg19: chr16-89989681;