Variant 18-12325353-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BS1BS2

The NM_032525.3(TUBB6):c.564G>A(p.Ser188=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000596 in 1,614,136 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.00058 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00060 ( 8 hom. )

Consequence

TUBB6
NM_032525.3 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -8.65

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.76).

BP6

Variant 18-12325353-G-A is Benign according to our data. Variant chr18-12325353-G-A is described in ClinVar as [Benign]. Clinvar id is 3048769.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-8.65 with no splicing effect.

BS1

Variant frequency is greater than expected in population eas. gnomad4_exome allele frequency = 0.000597 (873/1461888) while in subpopulation EAS AF= 0.0165 (656/39700). AF 95% confidence interval is 0.0155. There are 8 homozygotes in gnomad4_exome. There are 456 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High AC in GnomAd4 at 89 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TUBB6	NM_032525.3 linkuse as main transcript	c.564G>A	p.Ser188=	synonymous_variant	4/4	ENST00000317702.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TUBB6	ENST00000317702.10 linkuse as main transcript	c.564G>A	p.Ser188=	synonymous_variant	4/4	1	NM_032525.3	P1

Frequencies

GnomAD3 genomes

AF:

0.000578

AC:

AN:

152130

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.0148

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00158

AC:

397

AN:

251490

Hom.:

AF XY:

0.00146

AC XY:

199

AN XY:

135922

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.000198

Gnomad EAS exome

AF:

0.0185

Gnomad SAS exome

AF:

0.00127

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000114

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000597

AC:

873

AN:

1461888

Hom.:

Cov.:

AF XY:

0.000627

AC XY:

456

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.000306

Gnomad4 EAS exome

AF:

0.0165

Gnomad4 SAS exome

AF:

0.00126

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000540

Gnomad4 OTH exome

AF:

0.000662

GnomAD4 genome

AF:

0.000585

AC:

AN:

152248

Hom.:

Cov.:

AF XY:

0.000685

AC XY:

AN XY:

74434

show subpopulations

Gnomad4 AFR

AF:

0.0000722

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.0151

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000178

Hom.:

Bravo

AF:

0.000990

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

TUBB6-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 08, 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

-0.76

CADD

Benign

0.60

DANN

Benign

0.91

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