Variant 5-179871526-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 1P and 10B. PP3BP4_StrongBP6_ModerateBS2

The NM_015043.4(TBC1D9B):c.2420G>A(p.Arg807Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00376 in 1,612,688 control chromosomes in the GnomAD database, including 20 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0025 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0039 ( 19 hom. )

Consequence

TBC1D9B
NM_015043.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 7.74

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 Benign. Variant got -9 ACMG points.

PP3

Multiple lines of computational evidence support a deleterious effect 6: BayesDel_noAF, Cadd, Dann, Eigen, MutationAssessor, phyloP100way_vertebrate [when FATHMM_MKL, MetaRNN, MutationTaster was below the threshold]

BP4

Computational evidence support a benign effect (MetaRNN=0.05273047).

BP6

Variant 5-179871526-C-T is Benign according to our data. Variant chr5-179871526-C-T is described in ClinVar as [Benign]. Clinvar id is 2656141.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 19 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TBC1D9B	NM_015043.4 linkuse as main transcript	c.2420G>A	p.Arg807Gln	missense_variant	15/21	ENST00000355235.8	NP_055858.2	Q66K14-2B3KM54
TBC1D9B	NM_198868.3 linkuse as main transcript	c.2420G>A	p.Arg807Gln	missense_variant	15/22		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.2420G>A	p.Arg807Gln	missense_variant	15/21	5	NM_015043.4	ENSP00000347375.3		Q66K14-2
TBC1D9B	ENST00000524222.2 linkuse as main transcript	c.188-6260G>A		intron_variant		5		ENSP00000428724.2		H0YB58

Frequencies

GnomAD3 genomes

AF:

0.00248

AC:

378

AN:

152236

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000603

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000720

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00565

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00411

Gnomad OTH

AF:

0.000958

GnomAD3 exomes

AF:

0.00324

AC:

807

AN:

249308

Hom.:

AF XY:

0.00312

AC XY:

420

AN XY:

134722

show subpopulations

Gnomad AFR exome

AF:

0.000252

Gnomad AMR exome

AF:

0.000233

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00685

Gnomad NFE exome

AF:

0.00552

Gnomad OTH exome

AF:

0.00394

GnomAD4 exome

AF:

0.00389

AC:

5684

AN:

1460334

Hom.:

Cov.:

AF XY:

0.00372

AC XY:

2703

AN XY:

726284

show subpopulations

Gnomad4 AFR exome

AF:

0.000299

Gnomad4 AMR exome

AF:

0.000336

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000233

Gnomad4 FIN exome

AF:

0.00771

Gnomad4 NFE exome

AF:

0.00460

Gnomad4 OTH exome

AF:

0.00232

GnomAD4 genome

AF:

0.00248

AC:

378

AN:

152354

Hom.:

Cov.:

AF XY:

0.00254

AC XY:

189

AN XY:

74504

show subpopulations

Gnomad4 AFR

AF:

0.000601

Gnomad4 AMR

AF:

0.000719

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00565

Gnomad4 NFE

AF:

0.00412

Gnomad4 OTH

AF:

0.000948

Alfa

AF:

0.00356

Hom.:

Bravo

AF:

0.00198

TwinsUK

AF:

0.00458

AC:

ALSPAC

AF:

0.00545

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00279

AC:

ExAC

AF:

0.00396

AC:

481

EpiCase

AF:

0.00338

EpiControl

AF:

0.00362

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Oct 01, 2022

TBC1D9B: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.37

BayesDel_addAF

Uncertain

0.022

BayesDel_noAF

Pathogenic

0.26

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.44

.;T

Eigen

Pathogenic

0.87

Eigen_PC

Pathogenic

0.82

FATHMM_MKL

Pathogenic

1.0

M_CAP

Uncertain

0.14

MetaRNN

Benign

0.053

T;T

MetaSVM

Uncertain

-0.11

MutationAssessor

Pathogenic

3.3

M;M

PrimateAI

Uncertain

0.61

PROVEAN

Uncertain

-3.4

D;D

REVEL

Uncertain

0.57

Sift

Uncertain

0.0010

D;D

Sift4G

Uncertain

0.0030

D;D

Polyphen

1.0

D;D

Vest4

0.99

MVP

0.81

MPC

0.83

ClinPred

0.13

GERP RS

5.2

RBP_binding_hub_radar

0.97

RBP_regulation_power_radar

2.7

Varity_R

0.68

gMVP

0.82

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