chr17-36166250-C-G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001001417.7(TBC1D3B):​c.1395G>C​(p.Glu465Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00049 ( 4 hom., cov: 19)
Exomes 𝑓: 0.000059 ( 9 hom. )
Failed GnomAD Quality Control

Consequence

TBC1D3B
NM_001001417.7 missense

Scores

2
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.05
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]

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=0.03831318).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TBC1D3BNM_001001417.7 linkc.1395G>C p.Glu465Asp missense_variant Exon 14 of 14 ENST00000611257.5 NP_001001417.6 A6NDS4
TBC1D3BXM_005257980.5 linkc.1578G>C p.Glu526Asp missense_variant Exon 14 of 14 XP_005258037.2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TBC1D3BENST00000611257.5 linkc.1395G>C p.Glu465Asp missense_variant Exon 14 of 14 1 NM_001001417.7 ENSP00000478473.1 A6NDS4
ENSG00000276241ENST00000617914.1 linkn.158-10945C>G intron_variant Intron 2 of 2 3

Frequencies

GnomAD3 genomes
AF:
0.00
AC:
59
AN:
121438
Hom.:
4
Cov.:
19
FAILED QC
Gnomad AFR
AF:
0.00144
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000154
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:
0.0000592
AC:
71
AN:
1198908
Hom.:
9
Cov.:
32
AF XY:
0.0000568
AC XY:
34
AN XY:
598460
show subpopulations
Gnomad4 AFR exome
AF:
0.00130
Gnomad4 AMR exome
AF:
0.000116
Gnomad4 ASJ exome
AF:
0.000401
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000101
Gnomad4 OTH exome
AF:
0.0000966
GnomAD4 genome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.000485
AC:
59
AN:
121558
Hom.:
4
Cov.:
19
AF XY:
0.000453
AC XY:
27
AN XY:
59646
show subpopulations
Gnomad4 AFR
AF:
0.00143
Gnomad4 AMR
AF:
0.000153
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

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Oct 05, 2021
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1395G>C (p.E465D) alteration is located in exon 14 (coding exon 13) of the TBC1D3G gene. This alteration results from a G to C substitution at nucleotide position 1395, causing the glutamic acid (E) at amino acid position 465 to be replaced by an aspartic acid (D). 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
-0.29
T
BayesDel_noAF
Benign
-0.65
CADD
Benign
10
DANN
Benign
0.89
DEOGEN2
Benign
0.0043
T
Eigen
Benign
-1.2
Eigen_PC
Benign
-1.4
FATHMM_MKL
Benign
0.25
N
LIST_S2
Benign
0.67
T
M_CAP
Benign
0.0019
T
MetaRNN
Benign
0.038
T
MetaSVM
Benign
-0.97
T
MutationAssessor
Benign
0.0
N
PrimateAI
Uncertain
0.52
T
Sift4G
Uncertain
0.021
D
Polyphen
0.030
B
Vest4
0.070
MutPred
0.26
Loss of catalytic residue at E465 (P = 0.0295);
MVP
0.043
ClinPred
0.068
T
Varity_R
0.12
gMVP
0.011

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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.

Other links and lift over

dbSNP: rs1248236662; hg19: chr17-34493630; API