Variant chr5-179893447-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_015043.4(TBC1D9B):c.598G>A(p.Val200Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00138 in 1,608,108 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00087 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0014 ( 2 hom. )

Consequence

TBC1D9B
NM_015043.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.27

Variant links:

Genes affected

TBC1D9B (HGNC:29097): (TBC1 domain family member 9B) Predicted to enable GTPase activator activity. Predicted to be involved in activation of GTPase activity and intracellular protein transport. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

TBC1D9B links:

TBC1D9B (HGNC:):

TBC1D9B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.19102654).

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TBC1D9B	NM_015043.4 linkuse as main transcript	c.598G>A	p.Val200Met	missense_variant	5/21	ENST00000355235.8	NP_055858.2	Q66K14-2B3KM54
TBC1D9B	NM_198868.3 linkuse as main transcript	c.598G>A	p.Val200Met	missense_variant	5/22		NP_942568.2	Q66K14-1B3KM54Q9BW24

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TBC1D9B	ENST00000355235.8 linkuse as main transcript	c.598G>A	p.Val200Met	missense_variant	5/21	5	NM_015043.4	ENSP00000347375.3		Q66K14-2

Frequencies

GnomAD3 genomes

AF:

0.000874

AC:

133

AN:

152238

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000458

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00157

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.000723

AC:

179

AN:

247450

Hom.:

AF XY:

0.000770

AC XY:

103

AN XY:

133726

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.000671

Gnomad ASJ exome

AF:

0.000103

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000434

Gnomad FIN exome

AF:

0.0000468

Gnomad NFE exome

AF:

0.00120

Gnomad OTH exome

AF:

0.000829

GnomAD4 exome

AF:

0.00143

AC:

2083

AN:

1455752

Hom.:

Cov.:

AF XY:

0.00142

AC XY:

1030

AN XY:

723310

show subpopulations

Gnomad4 AFR exome

AF:

0.000150

Gnomad4 AMR exome

AF:

0.000585

Gnomad4 ASJ exome

AF:

0.0000776

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000525

Gnomad4 FIN exome

AF:

0.0000564

Gnomad4 NFE exome

AF:

0.00178

Gnomad4 OTH exome

AF:

0.000565

GnomAD4 genome

AF:

0.000873

AC:

133

AN:

152356

Hom.:

Cov.:

AF XY:

0.000859

AC XY:

AN XY:

74498

show subpopulations

Gnomad4 AFR

AF:

0.000457

Gnomad4 AMR

AF:

0.000327

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00157

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.00113

Hom.:

Bravo

AF:

0.000759

TwinsUK

AF:

0.00189

AC:

ALSPAC

AF:

0.00130

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00128

AC:

ExAC

AF:

0.000667

AC:

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

Ambry Genetics

Aug 23, 2021

The c.598G>A (p.V200M) alteration is located in exon 5 (coding exon 5) of the TBC1D9B gene. This alteration results from a G to A substitution at nucleotide position 598, causing the valine (V) at amino acid position 200 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.22

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.43

.;T

Eigen

Uncertain

0.32

Eigen_PC

Uncertain

0.29

FATHMM_MKL

Uncertain

0.90

M_CAP

Uncertain

0.11

MetaRNN

Benign

0.19

T;T

MetaSVM

Uncertain

0.34

MutationAssessor

Benign

1.8

L;L

PrimateAI

Benign

0.47

PROVEAN

Benign

-1.4

N;N

REVEL

Uncertain

0.51

Sift

Benign

0.070

T;T

Sift4G

Uncertain

0.023

D;D

Polyphen

0.95

P;D

Vest4

0.44

MVP

0.88

MPC

0.62

ClinPred

0.15

GERP RS

4.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.086

gMVP

0.32

Splicing

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