Variant 9-137241379-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 1P and 2B. PP2BP4_Moderate

The NM_006088.6(TUBB4B):c.19T>G(p.Leu7Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0010 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

TUBB4B
NM_006088.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.441

Variant links:

Genes affected

TUBB4B (HGNC:20771): (tubulin beta 4B class IVb) Enables double-stranded RNA binding activity. Predicted to be involved in microtubule cytoskeleton organization and mitotic cell cycle. Located in microtubule. Implicated in Leber congenital amaurosis with early-onset deafness. [provided by Alliance of Genome Resources, Apr 2022]

TUBB4B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -1 ACMG points.

PP2

Missense variant where missense usually causes diseases, TUBB4B

BP4

Computational evidence support a benign effect (MetaRNN=0.21295905).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TUBB4B	NM_006088.6 linkuse as main transcript	c.19T>G	p.Leu7Val	missense_variant	1/4	ENST00000340384.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TUBB4B	ENST00000340384.5 linkuse as main transcript	c.19T>G	p.Leu7Val	missense_variant	1/4	1	NM_006088.6	P1
TUBB4B	ENST00000604929.1 linkuse as main transcript	n.92T>G		non_coding_transcript_exon_variant	1/3	1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

150798

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000296

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00104

AC:

1448

AN:

1389904

Hom.:

Cov.:

AF XY:

0.000995

AC XY:

689

AN XY:

692618

show subpopulations

Gnomad4 AFR exome

AF:

0.00164

Gnomad4 AMR exome

AF:

0.000892

Gnomad4 ASJ exome

AF:

0.00315

Gnomad4 EAS exome

AF:

0.00416

Gnomad4 SAS exome

AF:

0.000152

Gnomad4 FIN exome

AF:

0.00392

Gnomad4 NFE exome

AF:

0.000813

Gnomad4 OTH exome

AF:

0.00165

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000199

AC:

AN:

150918

Hom.:

Cov.:

AF XY:

0.0000136

AC XY:

AN XY:

73748

show subpopulations

Gnomad4 AFR

AF:

0.0000242

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000296

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Mendelics

May 04, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.069

BayesDel_noAF

Benign

-0.34

Cadd

Benign

Dann

Benign

0.74

DEOGEN2

Benign

0.17

Eigen

Benign

-0.84

Eigen_PC

Benign

-0.75

FATHMM_MKL

Benign

0.50

LIST_S2

Uncertain

0.91

M_CAP

Pathogenic

0.36

MetaRNN

Benign

0.21

MetaSVM

Benign

-0.88

MutationAssessor

Benign

0.56

MutationTaster

Benign

1.0

PrimateAI

Pathogenic

0.88

PROVEAN

Benign

-0.15

REVEL

Benign

0.15

Sift4G

Benign

0.38

Polyphen

0.0010

Vest4

0.40

MutPred

0.22

Gain of disorder (P = 0.2136);

MVP

0.88

ClinPred

0.094

GERP RS

3.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.24

gMVP

0.69

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