Variant rs13110318 details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001396959.1(TBC1D1):c.3689G>A(p.Arg1230Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0927 in 1,612,330 control chromosomes in the GnomAD database, including 7,434 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.087 ( 669 hom., cov: 32)

Exomes 𝑓: 0.093 ( 6765 hom. )

Consequence

TBC1D1
NM_001396959.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.24

Variant links:

Genes affected

TBC1D1 (HGNC:11578): (TBC1 domain family member 1) TBC1D1 is the founding member of a family of proteins sharing a 180- to 200-amino acid TBC domain presumed to have a role in regulating cell growth and differentiation. These proteins share significant homology with TRE2 (USP6; MIM 604334), yeast Bub2, and CDC16 (MIM 603461) (White et al., 2000 [PubMed 10965142]).[supplied by OMIM, Mar 2008]

TBC1D1 links:

TBC1D1 (HGNC:):

TBC1D1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0014815629).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.141 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TBC1D1	NM_001396959.1 linkuse as main transcript	c.3689G>A	p.Arg1230Gln	missense_variant	22/22	ENST00000698857.1	NP_001383888.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TBC1D1	ENST00000698857.1 linkuse as main transcript	c.3689G>A	p.Arg1230Gln	missense_variant	22/22		NM_001396959.1	ENSP00000513987.1		A0A8V8TNS9

Frequencies

GnomAD3 genomes

AF:

0.0870

AC:

13239

AN:

152096

Hom.:

666

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0511

Gnomad AMI

AF:

0.181

Gnomad AMR

AF:

0.145

Gnomad ASJ

AF:

0.0986

Gnomad EAS

AF:

0.114

Gnomad SAS

AF:

0.0497

Gnomad FIN

AF:

0.119

Gnomad MID

AF:

0.0886

Gnomad NFE

AF:

0.0893

Gnomad OTH

AF:

0.0974

GnomAD3 exomes

AF:

0.104

AC:

25956

AN:

250600

Hom.:

1652

AF XY:

0.0983

AC XY:

13345

AN XY:

135698

show subpopulations

Gnomad AFR exome

AF:

0.0503

Gnomad AMR exome

AF:

0.193

Gnomad ASJ exome

AF:

0.101

Gnomad EAS exome

AF:

0.119

Gnomad SAS exome

AF:

0.0544

Gnomad FIN exome

AF:

0.119

Gnomad NFE exome

AF:

0.0916

Gnomad OTH exome

AF:

0.109

GnomAD4 exome

AF:

0.0932

AC:

136151

AN:

1460116

Hom.:

6765

Cov.:

AF XY:

0.0915

AC XY:

66459

AN XY:

726352

show subpopulations

Gnomad4 AFR exome

AF:

0.0504

Gnomad4 AMR exome

AF:

0.187

Gnomad4 ASJ exome

AF:

0.101

Gnomad4 EAS exome

AF:

0.117

Gnomad4 SAS exome

AF:

0.0522

Gnomad4 FIN exome

AF:

0.119

Gnomad4 NFE exome

AF:

0.0917

Gnomad4 OTH exome

AF:

0.0929

GnomAD4 genome

AF:

0.0870

AC:

13250

AN:

152214

Hom.:

669

Cov.:

AF XY:

0.0885

AC XY:

6588

AN XY:

74422

show subpopulations

Gnomad4 AFR

AF:

0.0511

Gnomad4 AMR

AF:

0.146

Gnomad4 ASJ

AF:

0.0986

Gnomad4 EAS

AF:

0.114

Gnomad4 SAS

AF:

0.0498

Gnomad4 FIN

AF:

0.119

Gnomad4 NFE

AF:

0.0893

Gnomad4 OTH

AF:

0.0959

Alfa

AF:

0.0883

Hom.:

1125

Bravo

AF:

0.0910

TwinsUK

AF:

0.0963

AC:

357

ALSPAC

AF:

0.0874

AC:

337

ESP6500AA

AF:

0.0536

AC:

236

ESP6500EA

AF:

0.0919

AC:

790

ExAC

AF:

0.0974

AC:

11828

Asia WGS

AF:

0.0820

AC:

286

AN:

3478

EpiCase

AF:

0.0922

EpiControl

AF:

0.0952

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.46

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.14

.;T;T

Eigen

Benign

-0.0064

Eigen_PC

Benign

-0.070

FATHMM_MKL

Uncertain

0.90

LIST_S2

Uncertain

0.90

D;D;D

MetaRNN

Benign

0.0015

T;T;T

MetaSVM

Benign

-0.87

MutationAssessor

Benign

1.7

.;L;.

PrimateAI

Benign

0.40

PROVEAN

Benign

-0.83

N;N;.

REVEL

Benign

0.098

Sift

Benign

0.30

T;T;.

Sift4G

Benign

0.23

T;T;T

Polyphen

0.45

.;P;.

Vest4

0.40

MPC

0.58

ClinPred

0.022

GERP RS

4.3

Varity_R

0.16

gMVP

0.35

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