Variant 18-12308378-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_032525.3(TUBB6):c.57+29C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.765 in 1,367,594 control chromosomes in the GnomAD database, including 405,189 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.67 ( 35851 hom., cov: 32)

Exomes 𝑓: 0.78 ( 369338 hom. )

Consequence

TUBB6
NM_032525.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.0950

Variant links:

Genes affected

TUBB6 (HGNC:20776): (tubulin beta 6 class V) Predicted to enable GTP binding activity. Predicted to be a structural constituent of cytoskeleton. Predicted to be involved in microtubule cytoskeleton organization and mitotic cell cycle. Located in microtubule. [provided by Alliance of Genome Resources, Apr 2022]

TUBB6 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.7).

BP6

Variant 18-12308378-C-A is Benign according to our data. Variant chr18-12308378-C-A is described in ClinVar as [Benign]. Clinvar id is 1684208.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.778 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TUBB6	NM_032525.3 linkuse as main transcript	c.57+29C>A		intron_variant		ENST00000317702.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TUBB6	ENST00000317702.10 linkuse as main transcript	c.57+29C>A		intron_variant		1	NM_032525.3	P1

Frequencies

GnomAD3 genomes

AF:

0.675

AC:

101802

AN:

150914

Hom.:

35839

Cov.:

show subpopulations

Gnomad AFR

AF:

0.467

Gnomad AMI

AF:

0.718

Gnomad AMR

AF:

0.629

Gnomad ASJ

AF:

0.744

Gnomad EAS

AF:

0.610

Gnomad SAS

AF:

0.770

Gnomad FIN

AF:

0.817

Gnomad MID

AF:

0.723

Gnomad NFE

AF:

0.783

Gnomad OTH

AF:

0.675

GnomAD3 exomes

AF:

0.763

AC:

79109

AN:

103704

Hom.:

30190

AF XY:

0.770

AC XY:

46659

AN XY:

60604

show subpopulations

Gnomad AFR exome

AF:

0.501

Gnomad AMR exome

AF:

0.629

Gnomad ASJ exome

AF:

0.754

Gnomad EAS exome

AF:

0.644

Gnomad SAS exome

AF:

0.791

Gnomad FIN exome

AF:

0.826

Gnomad NFE exome

AF:

0.801

Gnomad OTH exome

AF:

0.758

GnomAD4 exome

AF:

0.776

AC:

944557

AN:

1216574

Hom.:

369338

Cov.:

AF XY:

0.777

AC XY:

464684

AN XY:

598014

show subpopulations

Gnomad4 AFR exome

AF:

0.466

Gnomad4 AMR exome

AF:

0.614

Gnomad4 ASJ exome

AF:

0.756

Gnomad4 EAS exome

AF:

0.598

Gnomad4 SAS exome

AF:

0.792

Gnomad4 FIN exome

AF:

0.815

Gnomad4 NFE exome

AF:

0.791

Gnomad4 OTH exome

AF:

0.751

GnomAD4 genome

AF:

0.674

AC:

101831

AN:

151020

Hom.:

35851

Cov.:

AF XY:

0.676

AC XY:

49898

AN XY:

73796

show subpopulations

Gnomad4 AFR

AF:

0.467

Gnomad4 AMR

AF:

0.628

Gnomad4 ASJ

AF:

0.744

Gnomad4 EAS

AF:

0.610

Gnomad4 SAS

AF:

0.771

Gnomad4 FIN

AF:

0.817

Gnomad4 NFE

AF:

0.783

Gnomad4 OTH

AF:

0.677

Alfa

AF:

0.712

Hom.:

5734

Bravo

AF:

0.650

Asia WGS

AF:

0.661

AC:

2107

AN:

3192

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Facial palsy, congenital, with ptosis and velopharyngeal dysfunction

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Dec 05, 2021

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.70

CADD

Benign

7.4

DANN

Benign

0.72

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over