Variant 6-121090968-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_152730.6(TBC1D32):c.3539C>T(p.Thr1180Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0105 in 1,612,972 control chromosomes in the GnomAD database, including 109 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0074 ( 5 hom., cov: 32)

Exomes 𝑓: 0.011 ( 104 hom. )

Consequence

TBC1D32
NM_152730.6 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.78

Variant links:

Genes affected

TBC1D32 (HGNC:21485): (TBC1 domain family member 32) This gene encodes a TBC-domain containing protein. Studies of a similar protein in mouse and zebrafish suggest that the encoded protein is involved in sonic hedgehog signaling, and that it interacts with and stabilizes cell cycle-related kinase. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]

TBC1D32 links:

TBC1D32 (HGNC:):

TBC1D32 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0098257065).

BP6

Variant 6-121090968-G-A is Benign according to our data. Variant chr6-121090968-G-A is described in ClinVar as [Benign]. Clinvar id is 782999.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TBC1D32	NM_152730.6 linkuse as main transcript	c.3539C>T	p.Thr1180Ile	missense_variant	31/32	ENST00000398212.7	NP_689943.4	Q96NH3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TBC1D32	ENST00000398212.7 linkuse as main transcript	c.3539C>T	p.Thr1180Ile	missense_variant	31/32	5	NM_152730.6	ENSP00000381270.2	Q96NH3-1
TBC1D32	ENST00000275159.11 linkuse as main transcript	c.3662C>T	p.Thr1221Ile	missense_variant	32/33	5		ENSP00000275159.6	Q96NH3-4
TBC1D32	ENST00000464622.5 linkuse as main transcript	n.*4179C>T		non_coding_transcript_exon_variant	35/36	2		ENSP00000428839.1	Q96NH3-5
TBC1D32	ENST00000464622.5 linkuse as main transcript	n.*4179C>T		3_prime_UTR_variant	35/36	2		ENSP00000428839.1	Q96NH3-5

Frequencies

GnomAD3 genomes

AF:

0.00736

AC:

1116

AN:

151630

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00254

Gnomad AMI

AF:

0.0164

Gnomad AMR

AF:

0.00795

Gnomad ASJ

AF:

0.00923

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00291

Gnomad FIN

AF:

0.00220

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0116

Gnomad OTH

AF:

0.00768

GnomAD3 exomes

AF:

0.00699

AC:

1742

AN:

249182

Hom.:

AF XY:

0.00712

AC XY:

963

AN XY:

135214

show subpopulations

Gnomad AFR exome

AF:

0.00213

Gnomad AMR exome

AF:

0.00461

Gnomad ASJ exome

AF:

0.00894

Gnomad EAS exome

AF:

0.000111

Gnomad SAS exome

AF:

0.00369

Gnomad FIN exome

AF:

0.00327

Gnomad NFE exome

AF:

0.0108

Gnomad OTH exome

AF:

0.00794

GnomAD4 exome

AF:

0.0108

AC:

15839

AN:

1461224

Hom.:

104

Cov.:

AF XY:

0.0105

AC XY:

7620

AN XY:

726940

show subpopulations

Gnomad4 AFR exome

AF:

0.00179

Gnomad4 AMR exome

AF:

0.00476

Gnomad4 ASJ exome

AF:

0.0103

Gnomad4 EAS exome

AF:

0.0000505

Gnomad4 SAS exome

AF:

0.00417

Gnomad4 FIN exome

AF:

0.00286

Gnomad4 NFE exome

AF:

0.0127

Gnomad4 OTH exome

AF:

0.0104

GnomAD4 genome

AF:

0.00735

AC:

1116

AN:

151748

Hom.:

Cov.:

AF XY:

0.00719

AC XY:

533

AN XY:

74140

show subpopulations

Gnomad4 AFR

AF:

0.00254

Gnomad4 AMR

AF:

0.00794

Gnomad4 ASJ

AF:

0.00923

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00291

Gnomad4 FIN

AF:

0.00220

Gnomad4 NFE

AF:

0.0116

Gnomad4 OTH

AF:

0.00760

Alfa

AF:

0.0102

Hom.:

Bravo

AF:

0.00783

TwinsUK

AF:

0.0156

AC:

ALSPAC

AF:

0.0145

AC:

ESP6500AA

AF:

0.00110

AC:

ESP6500EA

AF:

0.0109

AC:

ExAC

AF:

0.00705

AC:

852

Asia WGS

AF:

0.00231

AC:

AN:

3476

EpiCase

AF:

0.0103

EpiControl

AF:

0.0112

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 08, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Benign

0.82

DEOGEN2

Benign

0.018

.;T

Eigen

Benign

-0.16

Eigen_PC

Benign

0.034

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.77

T;T

MetaRNN

Benign

0.0098

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.6

.;L

PROVEAN

Benign

-0.62

N;N

REVEL

Benign

0.045

Sift

Benign

0.69

T;T

Sift4G

Benign

0.20

T;T

Polyphen

0.056

.;B

Vest4

0.49

MVP

0.27

MPC

0.045

ClinPred

0.012

GERP RS

5.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.071

gMVP

0.13

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