Genetic Variant TBC1D28:p.Arg28Gln (chr17-18641097-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_Strong

The NM_001039397.3(TBC1D28):c.83G>A(p.Arg28Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000016 ( 0 hom., cov: 14)

Exomes 𝑓: 0.0000089 ( 0 hom. )

Consequence

TBC1D28
NM_001039397.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0150

Publications

0 publications found

Variant links:

Genes affected

TBC1D28 (HGNC:26858): (TBC1 domain family member 28) Predicted to enable GTPase activator activity. Predicted to be involved in activation of GTPase activity and intracellular protein transport. [provided by Alliance of Genome Resources, Apr 2022]

TBC1D28 links:

ENSG00000287058 (HGNC:):

ENSG00000287058 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=0.05500391).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001039397.3. 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
	TBC1D28	NM_001039397.3	MANE Select	c.83G>A	p.Arg28Gln	missense	Exon 5 of 10	NP_001034486.2	Q2M2D7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TBC1D28	ENST00000405044.7	TSL:5 MANE Select	c.83G>A	p.Arg28Gln	missense	Exon 5 of 10	ENSP00000385821.1	Q2M2D7
TBC1D28	ENST00000345096.8	TSL:2	c.83G>A	p.Arg28Gln	missense	Exon 4 of 9	ENSP00000339973.4	Q2M2D7
TBC1D28	ENST00000575220.5	TSL:5	c.83G>A	p.Arg28Gln	missense	Exon 6 of 7	ENSP00000458676.1	I3L197

Frequencies

GnomAD3 genomes

AF:

0.0000163

AC:

AN:

122858

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000325

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:

0.0000169

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000403

AC:

AN:

74492

AF XY:

0.0000271

show subpopulations

Gnomad AFR exome

AF:

0.000334

Gnomad AMR exome

AF:

0.0000826

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000888

AC:

AN:

563216

Hom.:

Cov.:

AF XY:

0.00000342

AC XY:

AN XY:

292634

show subpopulations

African (AFR)

AF:

0.000212

AC:

AN:

14172

American (AMR)

AF:

0.0000469

AC:

AN:

21314

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14778

East Asian (EAS)

AF:

0.00

AC:

AN:

31500

South Asian (SAS)

AF:

0.00

AC:

AN:

48642

European-Finnish (FIN)

AF:

0.00

AC:

AN:

42736

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2190

European-Non Finnish (NFE)

AF:

0.00000279

AC:

AN:

358340

Other (OTH)

AF:

0.00

AC:

AN:

29544

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.435

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

AF:

0.0000163

AC:

AN:

122858

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

57880

show subpopulations

African (AFR)

AF:

0.0000325

AC:

AN:

30768

American (AMR)

AF:

0.00

AC:

AN:

11760

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3172

East Asian (EAS)

AF:

0.00

AC:

AN:

4040

South Asian (SAS)

AF:

0.00

AC:

AN:

3216

European-Finnish (FIN)

AF:

0.00

AC:

AN:

7936

Middle Eastern (MID)

AF:

0.00

AC:

AN:

302

European-Non Finnish (NFE)

AF:

0.0000169

AC:

AN:

59308

Other (OTH)

AF:

0.00

AC:

AN:

1552

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000712

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

0.083

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.63

CADD

Benign

0.14

(source)

DANN

Benign

0.41

DEOGEN2

Benign

0.018

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.0016

LIST_S2

Benign

0.67

M_CAP

Benign

0.0013

MetaRNN

Benign

0.055

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.38

PhyloP100

-0.015

PROVEAN

Benign

-0.88

REVEL

Benign

0.071

Sift

Benign

0.14

Sift4G

Uncertain

0.052

Polyphen

0.90

Vest4

0.067

MutPred

0.38

Loss of helix (P = 0.0167)

MVP

0.040

MPC

0.43

ClinPred

0.019

GERP RS

-1.0

Varity_R

0.051

gMVP

0.024

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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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