Genetic Variant TBC1D3B:p.Leu382Phe (chr17-36166501-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001001417.7(TBC1D3B):c.1144C>T(p.Leu382Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 11/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 0)

Exomes 𝑓: 0.00012 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

TBC1D3B
NM_001001417.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0460

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 -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.096416086).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBC1D3B	NM_001001417.7 link	c.1144C>T	p.Leu382Phe	missense_variant	Exon 14 of 14	ENST00000611257.5	NP_001001417.6	A6NDS4
TBC1D3B	XM_005257980.5 link	c.1327C>T	p.Leu443Phe	missense_variant	Exon 14 of 14		XP_005258037.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TBC1D3B	ENST00000611257.5 link	c.1144C>T	p.Leu382Phe	missense_variant	Exon 14 of 14	1	NM_001001417.7	ENSP00000478473.1		A6NDS4
ENSG00000276241	ENST00000617914.1 link	n.158-10694G>A		intron_variant	Intron 2 of 2	3

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

30714

Hom.:

Cov.:

FAILED QC

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000120

AC:

AN:

490234

Hom.:

Cov.:

AF XY:

0.000155

AC XY:

AN XY:

244802

show subpopulations

Gnomad4 AFR exome

AF:

0.00204

Gnomad4 AMR exome

AF:

0.0000922

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000484

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000584

Gnomad4 OTH exome

AF:

0.0000983

GnomAD4 genome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

30714

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

14950

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:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000253

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Aug 12, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1144C>T (p.L382F) alteration is located in exon 14 (coding exon 13) of the TBC1D3G gene. This alteration results from a C to T substitution at nucleotide position 1144, causing the leucine (L) at amino acid position 382 to be replaced by a phenylalanine (F). 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

0.096

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.70

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.023

Eigen

Benign

-0.78

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.0015

LIST_S2

Benign

0.69

M_CAP

Benign

0.0019

MetaRNN

Benign

0.096

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.55

PrimateAI

Uncertain

0.50

Sift4G

Uncertain

0.014

Polyphen

0.91

Vest4

0.086

MutPred

0.20

Gain of methylation at K380 (P = 0.086);

MVP

0.043

ClinPred

0.24

Varity_R

0.094

gMVP

0.017

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