Variant chr5-179863794-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_015043.4(TBC1D9B):c.3356A>G(p.Gln1119Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000464 in 1,613,626 control chromosomes in the GnomAD database, including 1 homozygotes. 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.00029 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00048 ( 1 hom. )

Consequence

TBC1D9B
NM_015043.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.78

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.01459825).

BP6

Variant 5-179863794-T-C is Benign according to our data. Variant chr5-179863794-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2369072.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TBC1D9B	NM_015043.4 linkuse as main transcript	c.3356A>G	p.Gln1119Arg	missense_variant	21/21	ENST00000355235.8	NP_055858.2	Q66K14-2B3KM54
TBC1D9B	NM_198868.3 linkuse as main transcript	c.3407A>G	p.Gln1136Arg	missense_variant	22/22		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.3356A>G	p.Gln1119Arg	missense_variant	21/21	5	NM_015043.4	ENSP00000347375.3		Q66K14-2
TBC1D9B	ENST00000524222.2 linkuse as main transcript	c.*340A>G		3_prime_UTR_variant	4/4	5		ENSP00000428724.2		H0YB58

Frequencies

GnomAD3 genomes

AF:

0.000289

AC:

AN:

152060

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

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:

0.000618

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000203

AC:

AN:

251232

Hom.:

AF XY:

0.000214

AC XY:

AN XY:

135830

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000414

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000482

AC:

705

AN:

1461448

Hom.:

Cov.:

AF XY:

0.000461

AC XY:

335

AN XY:

727030

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

Gnomad4 AMR exome

AF:

0.0000447

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000614

Gnomad4 OTH exome

AF:

0.000282

GnomAD4 genome

AF:

0.000289

AC:

AN:

152178

Hom.:

Cov.:

AF XY:

0.000228

AC XY:

AN XY:

74406

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000618

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000445

Hom.:

Bravo

AF:

0.000272

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000814

AC:

ExAC

AF:

0.000173

AC:

EpiCase

AF:

0.000382

EpiControl

AF:

0.000474

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 08, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.060

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.63

CADD

Benign

0.14

DANN

Benign

0.54

DEOGEN2

Benign

0.0097

T;.;T

Eigen

Benign

-0.99

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.032

M_CAP

Benign

0.0077

MetaRNN

Benign

0.015

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.14

.;.;N

PrimateAI

Benign

0.25

PROVEAN

Benign

-0.64

N;N;N

REVEL

Benign

0.0080

Sift

Benign

0.64

T;T;T

Sift4G

Benign

0.58

T;T;T

Polyphen

0.0

.;B;B

Vest4

0.044

MVP

0.39

MPC

0.21

ClinPred

0.0043

GERP RS

-2.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Varity_R

0.024

gMVP

0.14

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