Genetic Variant TBC1D3I:p.Gly126Arg (chr17-36260240-C-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_001291463.2(TBC1D3I):c.376G>A(p.Gly126Arg) 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 Likely benign (★).

Frequency

Genomes: not found (cov: 0)

Exomes 𝑓: 0.0000029 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

TBC1D3I
NM_001291463.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.37

Publications

0 publications found

Variant links:

Genes affected

TBC1D3I (HGNC:32709): (TBC1 domain family member 3I) Predicted to enable GTPase activator activity. Predicted to be involved in activation of GTPase activity and intracellular protein transport. Predicted to be located in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

TBC1D3I links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0026156902).

BP6

Variant 17-36260240-C-T is Benign according to our data. Variant chr17-36260240-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3026214.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001291463.2. 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
	TBC1D3I	NM_001291463.2	MANE Select	c.376G>A	p.Gly126Arg	missense	Exon 6 of 14	NP_001278392.1	A0A087WXS9

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TBC1D3I	ENST00000621034.2	TSL:1 MANE Select	c.376G>A	p.Gly126Arg	missense	Exon 6 of 14	ENSP00000481258.1	A0A087WXS9
TBC1D3I	ENST00000618620.4	TSL:1	c.376G>A	p.Gly126Arg	missense	Exon 6 of 12	ENSP00000479474.1	A0A0B4J2F4
TBC1D3I	ENST00000616671.4	TSL:5	c.376G>A	p.Gly126Arg	missense	Exon 5 of 11	ENSP00000482914.1	A0A0B4J2F4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00125

AC:

AN:

19270

AF XY:

0.000627

show subpopulations

Gnomad AFR exome

AF:

0.000343

Gnomad AMR exome

AF:

0.00119

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00142

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00296

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000295

AC:

AN:

339388

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

169526

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:

6428

American (AMR)

AF:

0.00

AC:

AN:

28696

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

5696

East Asian (EAS)

AF:

0.00

AC:

AN:

18746

South Asian (SAS)

AF:

0.00

AC:

AN:

27950

European-Finnish (FIN)

AF:

0.00

AC:

AN:

13768

Middle Eastern (MID)

AF:

0.00

AC:

AN:

934

European-Non Finnish (NFE)

AF:

0.00000449

AC:

AN:

222934

Other (OTH)

AF:

0.00

AC:

AN:

14236

⚠️ 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: 0.375

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

Cov.:

ExAC

AF:

0.543

AC:

1229

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

-0.26

BayesDel_noAF

Benign

-0.61

CADD

Benign

3.1

(source)

DANN

Benign

0.67

DEOGEN2

Benign

0.050

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.14

MetaRNN

Benign

0.0026

MetaSVM

Benign

-1.1

PhyloP100

2.4

PrimateAI

Uncertain

0.71

Sift4G

Benign

0.29

Vest4

0.048

ClinPred

0.0066

GERP RS

-0.093

Varity_R

0.081

gMVP

0.024

Mutation Taster

=100/0

polymorphism

(source)

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

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