Variant rs16958445 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_153356.3(TBC1D21):c.338G>A(p.Arg113Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0166 in 1,614,184 control chromosomes in the GnomAD database, including 1,354 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.015 ( 121 hom., cov: 32)

Exomes 𝑓: 0.017 ( 1233 hom. )

Consequence

TBC1D21
NM_153356.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.284

Variant links:

Genes affected

TBC1D21 (HGNC:28536): (TBC1 domain family member 21) Predicted to enable GTPase activator activity. Predicted to be involved in activation of GTPase activity and intracellular protein transport. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

TBC1D21 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0015442073).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.144 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TBC1D21	NM_153356.3 linkuse as main transcript	c.338G>A	p.Arg113Gln	missense_variant	4/11	ENST00000300504.7	NP_699187.1	Q8IYX1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TBC1D21	ENST00000300504.7 linkuse as main transcript	c.338G>A	p.Arg113Gln	missense_variant	4/11	1	NM_153356.3	ENSP00000300504.2	Q8IYX1-1
TBC1D21	ENST00000535547.6 linkuse as main transcript	c.230G>A	p.Arg77Gln	missense_variant	3/10	1		ENSP00000439325.2	Q8IYX1-2
TBC1D21	ENST00000562056.1 linkuse as main transcript	c.338G>A	p.Arg113Gln	missense_variant	4/10	5		ENSP00000457096.1	H3BTA9

Frequencies

GnomAD3 genomes

AF:

0.0149

AC:

2264

AN:

152208

Hom.:

123

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00236

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00543

Gnomad ASJ

AF:

0.0349

Gnomad EAS

AF:

0.153

Gnomad SAS

AF:

0.119

Gnomad FIN

AF:

0.0142

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00600

Gnomad OTH

AF:

0.0158

GnomAD3 exomes

AF:

0.0323

AC:

8128

AN:

251484

Hom.:

475

AF XY:

0.0360

AC XY:

4892

AN XY:

135914

show subpopulations

Gnomad AFR exome

AF:

0.00172

Gnomad AMR exome

AF:

0.00367

Gnomad ASJ exome

AF:

0.0377

Gnomad EAS exome

AF:

0.153

Gnomad SAS exome

AF:

0.118

Gnomad FIN exome

AF:

0.0137

Gnomad NFE exome

AF:

0.00614

Gnomad OTH exome

AF:

0.0293

GnomAD4 exome

AF:

0.0168

AC:

24545

AN:

1461858

Hom.:

1233

Cov.:

AF XY:

0.0197

AC XY:

14304

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.00161

Gnomad4 AMR exome

AF:

0.00407

Gnomad4 ASJ exome

AF:

0.0365

Gnomad4 EAS exome

AF:

0.149

Gnomad4 SAS exome

AF:

0.113

Gnomad4 FIN exome

AF:

0.0136

Gnomad4 NFE exome

AF:

0.00461

Gnomad4 OTH exome

AF:

0.0286

GnomAD4 genome

AF:

0.0148

AC:

2257

AN:

152326

Hom.:

121

Cov.:

AF XY:

0.0178

AC XY:

1326

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.00236

Gnomad4 AMR

AF:

0.00542

Gnomad4 ASJ

AF:

0.0349

Gnomad4 EAS

AF:

0.153

Gnomad4 SAS

AF:

0.119

Gnomad4 FIN

AF:

0.0142

Gnomad4 NFE

AF:

0.00600

Gnomad4 OTH

AF:

0.0151

Alfa

AF:

0.0124

Hom.:

114

Bravo

AF:

0.0124

TwinsUK

AF:

0.00270

AC:

ALSPAC

AF:

0.00519

AC:

ESP6500AA

AF:

0.00273

AC:

ESP6500EA

AF:

0.00698

AC:

ExAC

AF:

0.0328

AC:

3988

Asia WGS

AF:

0.151

AC:

525

AN:

3478

EpiCase

AF:

0.00872

EpiControl

AF:

0.00717

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.82

BayesDel_noAF

Benign

-0.82

CADD

Benign

DANN

Benign

0.92

DEOGEN2

Benign

0.0086

.;T;T

Eigen

Benign

-0.83

Eigen_PC

Benign

-0.70

FATHMM_MKL

Benign

0.54

LIST_S2

Benign

0.68

T;T;T

MetaRNN

Benign

0.0015

T;T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

0.0

.;N;.

PrimateAI

Benign

0.23

PROVEAN

Benign

-0.26

N;N;N

REVEL

Benign

0.024

Sift

Benign

0.26

T;T;T

Sift4G

Benign

0.41

T;T;T

Polyphen

0.0020

.;B;.

Vest4

0.12

MPC

0.28

ClinPred

0.0070

GERP RS

0.33

Varity_R

0.029

gMVP

0.18

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over