Variant 18-12308246-C-T 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.-47C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.765 in 1,347,228 control chromosomes in the GnomAD database, including 398,993 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.67 ( 35168 hom., cov: 32)

Exomes 𝑓: 0.78 ( 363825 hom. )

Consequence

TUBB6
NM_032525.3 5_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.148

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=-0.75).

BP6

Variant 18-12308246-C-T is Benign according to our data. Variant chr18-12308246-C-T is described in ClinVar as [Benign]. Clinvar id is 1684205.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.777 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.-47C>T		5_prime_UTR_variant	1/4	ENST00000317702.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TUBB6	ENST00000317702.10 linkuse as main transcript	c.-47C>T		5_prime_UTR_variant	1/4	1	NM_032525.3	P1

Frequencies

GnomAD3 genomes

AF:

0.673

AC:

100152

AN:

148762

Hom.:

35157

Cov.:

show subpopulations

Gnomad AFR

AF:

0.468

Gnomad AMI

AF:

0.709

Gnomad AMR

AF:

0.629

Gnomad ASJ

AF:

0.743

Gnomad EAS

AF:

0.605

Gnomad SAS

AF:

0.770

Gnomad FIN

AF:

0.817

Gnomad MID

AF:

0.725

Gnomad NFE

AF:

0.782

Gnomad OTH

AF:

0.673

GnomAD3 exomes

AF:

0.748

AC:

64245

AN:

85892

Hom.:

24393

AF XY:

0.759

AC XY:

37557

AN XY:

49506

show subpopulations

Gnomad AFR exome

AF:

0.494

Gnomad AMR exome

AF:

0.591

Gnomad ASJ exome

AF:

0.749

Gnomad EAS exome

AF:

0.651

Gnomad SAS exome

AF:

0.789

Gnomad FIN exome

AF:

0.818

Gnomad NFE exome

AF:

0.803

Gnomad OTH exome

AF:

0.738

GnomAD4 exome

AF:

0.776

AC:

930172

AN:

1198358

Hom.:

363825

Cov.:

AF XY:

0.777

AC XY:

458477

AN XY:

590166

show subpopulations

Gnomad4 AFR exome

AF:

0.469

Gnomad4 AMR exome

AF:

0.603

Gnomad4 ASJ exome

AF:

0.754

Gnomad4 EAS exome

AF:

0.607

Gnomad4 SAS exome

AF:

0.782

Gnomad4 FIN exome

AF:

0.814

Gnomad4 NFE exome

AF:

0.792

Gnomad4 OTH exome

AF:

0.753

GnomAD4 genome

AF:

0.673

AC:

100181

AN:

148870

Hom.:

35168

Cov.:

AF XY:

0.675

AC XY:

48962

AN XY:

72588

show subpopulations

Gnomad4 AFR

AF:

0.468

Gnomad4 AMR

AF:

0.629

Gnomad4 ASJ

AF:

0.743

Gnomad4 EAS

AF:

0.606

Gnomad4 SAS

AF:

0.771

Gnomad4 FIN

AF:

0.817

Gnomad4 NFE

AF:

0.782

Gnomad4 OTH

AF:

0.675

Alfa

AF:

0.716

Hom.:

4660

Bravo

AF:

0.651

Asia WGS

AF:

0.655

AC:

2042

AN:

3122

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

-0.75

CADD

Benign

7.2

DANN

Benign

0.87

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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