Variant 4-37902259-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001396959.1(TBC1D1):c.164C>T(p.Thr55Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000265 in 1,613,994 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0015 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00014 ( 0 hom. )

Consequence

TBC1D1
NM_001396959.1 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.01

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 Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.005847335).

BP6

Variant 4-37902259-C-T is Benign according to our data. Variant chr4-37902259-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3046866.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TBC1D1	NM_001396959.1 linkuse as main transcript	c.164C>T	p.Thr55Ile	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.164C>T	p.Thr55Ile	missense_variant	2/22		NM_001396959.1	A2
TBC1D1	ENST00000261439.9 linkuse as main transcript	c.164C>T	p.Thr55Ile	missense_variant	2/20	1		P2	Q86TI0-1
TBC1D1	ENST00000508802.5 linkuse as main transcript	c.164C>T	p.Thr55Ile	missense_variant	2/21	2			Q86TI0-2
TBC1D1	ENST00000402522.1 linkuse as main transcript	c.164C>T	p.Thr55Ile	missense_variant	2/3	2

Frequencies

GnomAD3 genomes

AF:

0.00147

AC:

224

AN:

151988

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00529

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000197

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:

0.00

Gnomad OTH

AF:

0.000957

GnomAD3 exomes

AF:

0.000398

AC:

100

AN:

251440

Hom.:

AF XY:

0.000294

AC XY:

AN XY:

135902

show subpopulations

Gnomad AFR exome

AF:

0.00554

Gnomad AMR exome

AF:

0.000260

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000879

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000139

AC:

203

AN:

1461888

Hom.:

Cov.:

AF XY:

0.000106

AC XY:

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.00469

Gnomad4 AMR exome

AF:

0.000402

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000989

Gnomad4 OTH exome

AF:

0.000281

GnomAD4 genome

AF:

0.00147

AC:

224

AN:

152106

Hom.:

Cov.:

AF XY:

0.00144

AC XY:

107

AN XY:

74340

show subpopulations

Gnomad4 AFR

AF:

0.00528

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000947

Alfa

AF:

0.000295

Hom.:

Bravo

AF:

0.00165

ESP6500AA

AF:

0.00386

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000486

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

TBC1D1-related disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 11, 2020

This variant is classified as likely 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

0.093

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.61

Cadd

Benign

Dann

Uncertain

0.98

Eigen

Benign

-0.49

Eigen_PC

Benign

-0.33

FATHMM_MKL

Benign

0.48

LIST_S2

Benign

0.69

T;T;T

M_CAP

Benign

0.0051

MetaRNN

Benign

0.0058

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

N;N;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.37

PROVEAN

Benign

-0.34

N;N;N

REVEL

Benign

0.094

Sift

Benign

0.10

T;T;T

Sift4G

Benign

0.16

T;T;T

Polyphen

0.0

.;B;.

Vest4

0.095

MVP

0.39

MPC

0.57

ClinPred

0.017

GERP RS

5.2

Varity_R

0.036

gMVP

0.10

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over