17-36171907-T-C

Variant summary

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

The NM_001001417.7(TBC1D3B):​c.445A>G​(p.Ile149Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000134 in 149,292 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., cov: 24)
Exomes 𝑓: 0.000064 ( 6 hom. )
Failed GnomAD Quality Control

Consequence

TBC1D3B
NM_001001417.7 missense

Scores

2
14

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.150
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.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.051583827).
BP6
Variant 17-36171907-T-C is Benign according to our data. Variant chr17-36171907-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2345611.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TBC1D3BNM_001001417.7 linkc.445A>G p.Ile149Val missense_variant Exon 7 of 14 ENST00000611257.5 NP_001001417.6 A6NDS4
TBC1D3BXM_005257980.5 linkc.628A>G p.Ile210Val missense_variant Exon 7 of 14 XP_005258037.2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TBC1D3BENST00000611257.5 linkc.445A>G p.Ile149Val missense_variant Exon 7 of 14 1 NM_001001417.7 ENSP00000478473.1 A6NDS4
TBC1D3BENST00000622280.1 linkn.417A>G non_coding_transcript_exon_variant Exon 2 of 4 5
ENSG00000276241ENST00000617914.1 linkn.158-5288T>C intron_variant Intron 2 of 2 3

Frequencies

GnomAD3 genomes
AF:
0.000134
AC:
20
AN:
149176
Hom.:
0
Cov.:
24
show subpopulations
Gnomad AFR
AF:
0.0000726
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000469
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:
0.0000756
Gnomad OTH
AF:
0.00246
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.0000640
AC:
93
AN:
1453672
Hom.:
6
Cov.:
33
AF XY:
0.0000802
AC XY:
58
AN XY:
723392
show subpopulations
Gnomad4 AFR exome
AF:
0.0000300
Gnomad4 AMR exome
AF:
0.000134
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000504
Gnomad4 SAS exome
AF:
0.0000813
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000679
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.000134
AC:
20
AN:
149292
Hom.:
0
Cov.:
24
AF XY:
0.000110
AC XY:
8
AN XY:
72906
show subpopulations
Gnomad4 AFR
AF:
0.0000724
Gnomad4 AMR
AF:
0.000468
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000756
Gnomad4 OTH
AF:
0.00243

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

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

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
0.092
BayesDel_addAF
Benign
-0.36
T
BayesDel_noAF
Benign
-0.76
CADD
Benign
0.017
DANN
Benign
0.17
DEOGEN2
Benign
0.015
T
Eigen
Benign
-1.9
Eigen_PC
Benign
-1.9
FATHMM_MKL
Benign
0.012
N
LIST_S2
Benign
0.31
T
M_CAP
Uncertain
0.16
D
MetaRNN
Benign
0.052
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
-0.36
N
PrimateAI
Uncertain
0.71
T
Sift4G
Benign
1.0
T
Polyphen
0.0
B
Vest4
0.082
MutPred
0.39
Loss of disorder (P = 0.2077);
MVP
0.043
ClinPred
0.039
T
Varity_R
0.054
gMVP
0.021

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.12
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: rs201615087; hg19: chr17-34499266; API