Variant 18-12308794-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_032525.3(TUBB6):c.165G>C(p.Ser55=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 1,592,370 control chromosomes in the GnomAD database, including 10,387 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.11 ( 943 hom., cov: 33)

Exomes 𝑓: 0.11 ( 9444 hom. )

Consequence

TUBB6
NM_032525.3 splice_region, synonymous

Scores

Splicing: ADA: 0.0003294

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -4.04

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.65).

BP6

Variant 18-12308794-G-C is Benign according to our data. Variant chr18-12308794-G-C is described in ClinVar as [Benign]. Clinvar id is 1684209.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-4.04 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.152 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.165G>C	p.Ser55=	splice_region_variant, synonymous_variant	2/4	ENST00000317702.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TUBB6	ENST00000317702.10 linkuse as main transcript	c.165G>C	p.Ser55=	splice_region_variant, synonymous_variant	2/4	1	NM_032525.3	P1

Frequencies

GnomAD3 genomes

AF:

0.110

AC:

16687

AN:

152120

Hom.:

944

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0822

Gnomad AMI

AF:

0.129

Gnomad AMR

AF:

0.157

Gnomad ASJ

AF:

0.158

Gnomad EAS

AF:

0.159

Gnomad SAS

AF:

0.121

Gnomad FIN

AF:

0.0850

Gnomad MID

AF:

0.193

Gnomad NFE

AF:

0.111

Gnomad OTH

AF:

0.131

GnomAD3 exomes

AF:

0.126

AC:

31297

AN:

248668

Hom.:

2101

AF XY:

0.126

AC XY:

16962

AN XY:

134956

show subpopulations

Gnomad AFR exome

AF:

0.0806

Gnomad AMR exome

AF:

0.174

Gnomad ASJ exome

AF:

0.167

Gnomad EAS exome

AF:

0.157

Gnomad SAS exome

AF:

0.121

Gnomad FIN exome

AF:

0.0896

Gnomad NFE exome

AF:

0.116

Gnomad OTH exome

AF:

0.141

GnomAD4 exome

AF:

0.111

AC:

159369

AN:

1440132

Hom.:

9444

Cov.:

AF XY:

0.112

AC XY:

80498

AN XY:

717752

show subpopulations

Gnomad4 AFR exome

AF:

0.0785

Gnomad4 AMR exome

AF:

0.172

Gnomad4 ASJ exome

AF:

0.160

Gnomad4 EAS exome

AF:

0.183

Gnomad4 SAS exome

AF:

0.121

Gnomad4 FIN exome

AF:

0.0922

Gnomad4 NFE exome

AF:

0.105

Gnomad4 OTH exome

AF:

0.118

GnomAD4 genome

AF:

0.110

AC:

16689

AN:

152238

Hom.:

943

Cov.:

AF XY:

0.110

AC XY:

8196

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.0821

Gnomad4 AMR

AF:

0.157

Gnomad4 ASJ

AF:

0.158

Gnomad4 EAS

AF:

0.159

Gnomad4 SAS

AF:

0.120

Gnomad4 FIN

AF:

0.0850

Gnomad4 NFE

AF:

0.111

Gnomad4 OTH

AF:

0.130

Alfa

AF:

0.0915

Hom.:

261

Bravo

AF:

0.114

EpiCase

AF:

0.131

EpiControl

AF:

0.129

ClinVar

Significance: Benign

Submissions summary: Benign:3

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

- -

TUBB6-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 25, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.65

CADD

Benign

DANN

Benign

0.85

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00033

dbscSNV1_RF

Benign

0.010

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