Genetic Variant TBC1D3B:p.Ala206Thr (chr17-36169942-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_ModerateBP6_Moderate

The NM_001001417.7(TBC1D3B):c.616G>A(p.Ala206Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 10/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000074 ( 0 hom., cov: 5)

Exomes 𝑓: 0.00032 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

TBC1D3B
NM_001001417.7 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.99

Variant links:

Genes affected

TBC1D3B (HGNC:27011): (TBC1 domain family member 3B) This gene encodes a protein that is similar to TBC1 domain family, member 3. This protein contains a TBC (Tre-2, Bub2p, and Cdc16p) domain, which is found in proteins involved in RAB GTPase signaling and vesicle trafficking. There are multiple copies of this gene located within a cluster of chemokine genes on chromosome 17q. [provided by RefSeq, Apr 2009]

TBC1D3B links:

ENSG00000276241 (HGNC:):

ENSG00000276241 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.09531164).

BP6

Variant 17-36169942-C-T is Benign according to our data. Variant chr17-36169942-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2647681.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBC1D3B	NM_001001417.7 link	c.616G>A	p.Ala206Thr	missense_variant	Exon 9 of 14	ENST00000611257.5	NP_001001417.6	A6NDS4
TBC1D3B	XM_005257980.5 link	c.799G>A	p.Ala267Thr	missense_variant	Exon 9 of 14		XP_005258037.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
TBC1D3B	ENST00000611257.5 link	c.616G>A	p.Ala206Thr	missense_variant	Exon 9 of 14	1	NM_001001417.7	ENSP00000478473.1	A6NDS4
ENSG00000276241	ENST00000617914.1 link	n.158-7253C>T		intron_variant	Intron 2 of 2	3
TBC1D3B	ENST00000622280.1 link	n.*129G>A		downstream_gene_variant		5

Frequencies

GnomAD3 genomes

AF:

0.0000737

AC:

AN:

27152

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000580

AC:

AN:

125766

Hom.:

AF XY:

0.000639

AC XY:

AN XY:

70470

show subpopulations

Gnomad AFR exome

AF:

0.000138

Gnomad AMR exome

AF:

0.0000767

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000565

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00107

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000323

AC:

AN:

263446

Hom.:

Cov.:

AF XY:

0.000249

AC XY:

AN XY:

140458

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000599

Gnomad4 OTH exome

AF:

0.000210

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000736

AC:

AN:

27168

Hom.:

Cov.:

AF XY:

0.000159

AC XY:

AN XY:

12556

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000843

Hom.:

ESP6500AA

AF:

0.000435

AC:

ESP6500EA

AF:

0.00233

AC:

ExAC

AF:

0.00113

AC:

102

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Dec 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

TBC1D3B: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.014

BayesDel_noAF

Benign

-0.26

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.22

Eigen

Benign

0.010

Eigen_PC

Benign

-0.28

FATHMM_MKL

Benign

0.45

LIST_S2

Uncertain

0.94

M_CAP

Benign

0.0084

MetaRNN

Benign

0.095

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.6

PrimateAI

Uncertain

0.72

Sift4G

Uncertain

0.0020

Polyphen

1.0

Vest4

0.63

MVP

0.043

ClinPred

0.10

Varity_R

0.085

gMVP

0.12

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