Variant 5-179865331-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_015043.4(TBC1D9B):c.2944C>T(p.Arg982Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000614 in 1,614,070 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00038 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00064 ( 1 hom. )

Consequence

TBC1D9B
NM_015043.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.11

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 Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TBC1D9B	NM_015043.4 linkuse as main transcript	c.2944C>T	p.Arg982Trp	missense_variant	20/21	ENST00000355235.8	NP_055858.2	Q66K14-2B3KM54
TBC1D9B	NM_198868.3 linkuse as main transcript	c.2995C>T	p.Arg999Trp	missense_variant	21/22		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.2944C>T	p.Arg982Trp	missense_variant	20/21	5	NM_015043.4	ENSP00000347375.3		Q66K14-2
TBC1D9B	ENST00000524222.2 linkuse as main transcript	c.188-65C>T		intron_variant		5		ENSP00000428724.2		H0YB58

Frequencies

GnomAD3 genomes

AF:

0.000381

AC:

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

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:

0.000735

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000374

AC:

AN:

251396

Hom.:

AF XY:

0.000353

AC XY:

AN XY:

135864

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000173

Gnomad ASJ exome

AF:

0.000893

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000686

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000638

AC:

933

AN:

1461750

Hom.:

Cov.:

AF XY:

0.000608

AC XY:

442

AN XY:

727162

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.000179

Gnomad4 ASJ exome

AF:

0.000536

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000188

Gnomad4 NFE exome

AF:

0.000780

Gnomad4 OTH exome

AF:

0.000679

GnomAD4 genome

AF:

0.000381

AC:

AN:

152320

Hom.:

Cov.:

AF XY:

0.000349

AC XY:

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.000120

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000735

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000587

Hom.:

Bravo

AF:

0.000314

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000814

AC:

ExAC

AF:

0.000280

AC:

EpiCase

AF:

0.000709

EpiControl

AF:

0.000356

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

Jul 27, 2024

The c.2995C>T (p.R999W) alteration is located in exon 21 (coding exon 21) of the TBC1D9B gene. This alteration results from a C to T substitution at nucleotide position 2995, causing the arginine (R) at amino acid position 999 to be replaced by a tryptophan (W). 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

0.10

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.17

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.20

T;.;T

Eigen

Uncertain

0.45

Eigen_PC

Uncertain

0.37

FATHMM_MKL

Uncertain

0.81

M_CAP

Benign

0.062

MetaRNN

Uncertain

0.53

D;D;D

MetaSVM

Benign

-0.55

MutationAssessor

Uncertain

2.9

.;.;M

PrimateAI

Uncertain

0.51

PROVEAN

Pathogenic

-4.8

D;D;D

REVEL

Benign

0.18

Sift

Pathogenic

0.0

D;D;D

Sift4G

Pathogenic

0.0010

D;D;D

Polyphen

1.0, 1.0

.;D;D

Vest4

0.74

MVP

0.76

MPC

0.70

ClinPred

0.52

GERP RS

4.1

Varity_R

0.32

gMVP

0.40

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