Genetic Variant NM_001001417.7:c.1144C>T (chr17-36166501-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -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. 12/18 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

Publications

0 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001001417.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBC1D3B	NM_001001417.7	MANE Select	c.1144C>T	p.Leu382Phe	missense	Exon 14 of 14	NP_001001417.6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBC1D3B	ENST00000611257.5	TSL:1 MANE Select	c.1144C>T	p.Leu382Phe	missense	Exon 14 of 14	ENSP00000478473.1	A6NDS4
	ENSG00000276241	ENST00000617914.2	TSL:3	n.358-10694G>A		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

30714

Hom.:

Cov.:

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

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00204

AC:

AN:

7842

American (AMR)

AF:

0.0000922

AC:

AN:

32554

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

7376

East Asian (EAS)

AF:

0.00

AC:

AN:

26286

South Asian (SAS)

AF:

0.000484

AC:

AN:

37170

European-Finnish (FIN)

AF:

0.00

AC:

AN:

15004

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1222

European-Non Finnish (NFE)

AF:

0.0000584

AC:

AN:

342444

Other (OTH)

AF:

0.0000983

AC:

AN:

20336

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.358

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

African (AFR)

AF:

0.00

AC:

AN:

2736

American (AMR)

AF:

0.00

AC:

AN:

6304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

664

East Asian (EAS)

AF:

0.00

AC:

AN:

1904

South Asian (SAS)

AF:

0.00

AC:

AN:

938

European-Finnish (FIN)

AF:

0.00

AC:

AN:

2190

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

15374

Other (OTH)

AF:

0.00

AC:

AN:

420

Alfa

AF:

0.000253

Hom.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.096

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.70

CADD

Benign

(source)

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

PhyloP100

-0.046

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

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over