Variant 4-37902458-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_001396959.1(TBC1D1):c.363C>T(p.Asp121=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00172 in 1,613,840 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0018 ( 4 hom. )

Consequence

TBC1D1
NM_001396959.1 synonymous

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.0400

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 -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP6

Variant 4-37902458-C-T is Benign according to our data. Variant chr4-37902458-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 711939.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.04 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TBC1D1	NM_001396959.1 linkuse as main transcript	c.363C>T	p.Asp121=	synonymous_variant	2/22	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.363C>T	p.Asp121=	synonymous_variant	2/22		NM_001396959.1	ENSP00000513987	A2
TBC1D1	ENST00000261439.9 linkuse as main transcript	c.363C>T	p.Asp121=	synonymous_variant	2/20	1		ENSP00000261439	P2	Q86TI0-1
TBC1D1	ENST00000508802.5 linkuse as main transcript	c.363C>T	p.Asp121=	synonymous_variant	2/21	2		ENSP00000423651		Q86TI0-2
TBC1D1	ENST00000402522.1 linkuse as main transcript	c.363C>T	p.Asp121=	synonymous_variant	2/3	2		ENSP00000383994

Frequencies

GnomAD3 genomes

AF:

0.00113

AC:

172

AN:

152144

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000386

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.0000944

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00197

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00118

AC:

297

AN:

251090

Hom.:

AF XY:

0.00127

AC XY:

172

AN XY:

135688

show subpopulations

Gnomad AFR exome

AF:

0.000369

Gnomad AMR exome

AF:

0.00130

Gnomad ASJ exome

AF:

0.0000995

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000982

Gnomad FIN exome

AF:

0.000278

Gnomad NFE exome

AF:

0.00179

Gnomad OTH exome

AF:

0.000981

GnomAD4 exome

AF:

0.00178

AC:

2596

AN:

1461578

Hom.:

Cov.:

AF XY:

0.00172

AC XY:

1249

AN XY:

727072

show subpopulations

Gnomad4 AFR exome

AF:

0.000358

Gnomad4 AMR exome

AF:

0.00121

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000777

Gnomad4 FIN exome

AF:

0.000262

Gnomad4 NFE exome

AF:

0.00211

Gnomad4 OTH exome

AF:

0.00159

GnomAD4 genome

AF:

0.00113

AC:

172

AN:

152262

Hom.:

Cov.:

AF XY:

0.00109

AC XY:

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.000385

Gnomad4 AMR

AF:

0.000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00145

Gnomad4 FIN

AF:

0.0000944

Gnomad4 NFE

AF:

0.00197

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00186

Hom.:

Bravo

AF:

0.00126

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00180

EpiControl

AF:

0.00225

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Nov 01, 2023	TBC1D1: BP4, BP7 -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

4.2

DANN

Benign

0.34

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