Genetic Variant NM_001001417.7:c.616G>A (chr17-36169942-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -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. 11/18 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

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 -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 VariationId is 2647681.Status of the report is criteria_provided_single_submitter, 1 stars.

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.616G>A	p.Ala206Thr	missense	Exon 9 of 14	NP_001001417.6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TBC1D3B	ENST00000611257.5	TSL:1 MANE Select	c.616G>A	p.Ala206Thr	missense	Exon 9 of 14	ENSP00000478473.1	A6NDS4
ENSG00000276241	ENST00000617914.2	TSL:3	n.358-7253C>T		intron	N/A
TBC1D3B	ENST00000622280.1	TSL:5	n.*129G>A		downstream_gene	N/A

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

GnomAD2 exomes

AF:

0.000580

AC:

AN:

125766

AF XY:

0.000639

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 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

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

African (AFR)

AF:

0.00

AC:

AN:

9996

American (AMR)

AF:

0.00

AC:

AN:

14600

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

6260

East Asian (EAS)

AF:

0.00

AC:

AN:

23488

South Asian (SAS)

AF:

0.00

AC:

AN:

42658

European-Finnish (FIN)

AF:

0.00

AC:

AN:

14334

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1042

European-Non Finnish (NFE)

AF:

0.000599

AC:

AN:

136788

Other (OTH)

AF:

0.000210

AC:

AN:

14280

⚠️ 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: 0.348

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: AS_VQSR

AF:

0.0000736

AC:

AN:

27168

Hom.:

Cov.:

AF XY:

0.000159

AC XY:

AN XY:

12556

show subpopulations

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

African (AFR)

AF:

0.00

AC:

AN:

12954

American (AMR)

AF:

0.00

AC:

AN:

2974

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

460

East Asian (EAS)

AF:

0.00

AC:

AN:

2416

South Asian (SAS)

AF:

0.00

AC:

AN:

738

European-Finnish (FIN)

AF:

0.00

AC:

AN:

348

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.000294

AC:

AN:

6808

Other (OTH)

AF:

0.00

AC:

AN:

320

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 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: 0.250

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.0000843

Hom.:

ESP6500AA

AF:

0.000435

AC:

ESP6500EA

AF:

0.00233

AC:

ExAC

AF:

0.00113

AC:

102

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.014

BayesDel_noAF

Benign

-0.26

CADD

Benign

(source)

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

PhyloP100

3.0

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

Mutation Taster

=98/2

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over