Variant 4-37902468-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001396959.1(TBC1D1):c.373C>T(p.Arg125Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0922 in 1,612,780 control chromosomes in the GnomAD database, including 7,332 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.079 ( 590 hom., cov: 32)

Exomes 𝑓: 0.094 ( 6742 hom. )

Consequence

TBC1D1
NM_001396959.1 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.45

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0016258061).

BP6

Variant 4-37902468-C-T is Benign according to our data. Variant chr4-37902468-C-T is described in ClinVar as [Benign]. Clinvar id is 3058918.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.122 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TBC1D1	NM_001396959.1 linkuse as main transcript	c.373C>T	p.Arg125Trp	missense_variant	2/22	ENST00000698857.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TBC1D1	ENST00000698857.1 linkuse as main transcript	c.373C>T	p.Arg125Trp	missense_variant	2/22		NM_001396959.1	A2
TBC1D1	ENST00000261439.9 linkuse as main transcript	c.373C>T	p.Arg125Trp	missense_variant	2/20	1		P2	Q86TI0-1
TBC1D1	ENST00000508802.5 linkuse as main transcript	c.373C>T	p.Arg125Trp	missense_variant	2/21	2			Q86TI0-2
TBC1D1	ENST00000402522.1 linkuse as main transcript	c.373C>T	p.Arg125Trp	missense_variant	2/3	2

Frequencies

GnomAD3 genomes

AF:

0.0792

AC:

12038

AN:

151964

Hom.:

592

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0292

Gnomad AMI

AF:

0.168

Gnomad AMR

AF:

0.0694

Gnomad ASJ

AF:

0.132

Gnomad EAS

AF:

0.115

Gnomad SAS

AF:

0.132

Gnomad FIN

AF:

0.151

Gnomad MID

AF:

0.101

Gnomad NFE

AF:

0.0898

Gnomad OTH

AF:

0.0939

GnomAD3 exomes

AF:

0.0972

AC:

24354

AN:

250464

Hom.:

1325

AF XY:

0.0997

AC XY:

13501

AN XY:

135384

show subpopulations

Gnomad AFR exome

AF:

0.0267

Gnomad AMR exome

AF:

0.0770

Gnomad ASJ exome

AF:

0.139

Gnomad EAS exome

AF:

0.123

Gnomad SAS exome

AF:

0.125

Gnomad FIN exome

AF:

0.141

Gnomad NFE exome

AF:

0.0904

Gnomad OTH exome

AF:

0.0910

GnomAD4 exome

AF:

0.0936

AC:

136736

AN:

1460698

Hom.:

6742

Cov.:

AF XY:

0.0945

AC XY:

68670

AN XY:

726650

show subpopulations

Gnomad4 AFR exome

AF:

0.0263

Gnomad4 AMR exome

AF:

0.0770

Gnomad4 ASJ exome

AF:

0.139

Gnomad4 EAS exome

AF:

0.104

Gnomad4 SAS exome

AF:

0.123

Gnomad4 FIN exome

AF:

0.132

Gnomad4 NFE exome

AF:

0.0907

Gnomad4 OTH exome

AF:

0.0949

GnomAD4 genome

AF:

0.0791

AC:

12029

AN:

152082

Hom.:

590

Cov.:

AF XY:

0.0822

AC XY:

6111

AN XY:

74310

show subpopulations

Gnomad4 AFR

AF:

0.0291

Gnomad4 AMR

AF:

0.0694

Gnomad4 ASJ

AF:

0.132

Gnomad4 EAS

AF:

0.116

Gnomad4 SAS

AF:

0.131

Gnomad4 FIN

AF:

0.151

Gnomad4 NFE

AF:

0.0898

Gnomad4 OTH

AF:

0.0929

Alfa

AF:

0.0919

Hom.:

1379

Bravo

AF:

0.0719

TwinsUK

AF:

0.0895

AC:

332

ALSPAC

AF:

0.0802

AC:

309

ESP6500AA

AF:

0.0295

AC:

130

ESP6500EA

AF:

0.0966

AC:

831

ExAC

AF:

0.0939

AC:

11394

Asia WGS

AF:

0.109

AC:

379

AN:

3478

EpiCase

AF:

0.0908

EpiControl

AF:

0.0940

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

TBC1D1-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 17, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.63

Cadd

Benign

Dann

Uncertain

1.0

Eigen

Benign

-0.43

Eigen_PC

Benign

-0.48

FATHMM_MKL

Benign

0.22

LIST_S2

Uncertain

0.96

D;D;D

MetaRNN

Benign

0.0016

T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.69

N;N;.

MutationTaster

Benign

1.0

P;P;P

PrimateAI

Benign

0.23

PROVEAN

Benign

-1.4

N;N;D

REVEL

Benign

0.13

Sift

Uncertain

0.015

D;D;D

Sift4G

Uncertain

0.017

D;D;D

Polyphen

0.96

.;D;.

Vest4

0.21

MPC

1.0

ClinPred

0.019

GERP RS

3.1

Varity_R

0.059

gMVP

0.31

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over