rs118077502

Variant names:

Variant summary

Our verdict is Benign. The variant received -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. 14/20 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

Publications

8 publications found

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 Gene-Disease associations (from GenCC):

ciliopathy
Inheritance: AR Classification: DEFINITIVE, MODERATE Submitted by: Illumina, G2P
orofaciodigital syndrome
Inheritance: AR Classification: MODERATE Submitted by: Franklin by Genoox
orofaciodigital syndrome IX
Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

TBC1D32 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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,Unknown gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBC1D32	NM_152730.6 link	c.3539C>T	p.Thr1180Ile	missense_variant	Exon 31 of 32	ENST00000398212.7	NP_689943.4	Q96NH3-1

Ensembl

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

GnomAD2 exomes

AF:

0.00699

AC:

1742

AN:

249182

AF XY:

0.00712

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 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

African (AFR)

AF:

0.00179

AC:

AN:

33460

American (AMR)

AF:

0.00476

AC:

213

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.0103

AC:

269

AN:

26122

East Asian (EAS)

AF:

0.0000505

AC:

AN:

39610

South Asian (SAS)

AF:

0.00417

AC:

360

AN:

86228

European-Finnish (FIN)

AF:

0.00286

AC:

152

AN:

53234

Middle Eastern (MID)

AF:

0.00173

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.0127

AC:

14146

AN:

1111728

Other (OTH)

AF:

0.0104

AC:

627

AN:

60364

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.460

Heterozygous variant carriers

790

1580

2371

3161

3951

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00735

AC:

1116

AN:

151748

Hom.:

Cov.:

AF XY:

0.00719

AC XY:

533

AN XY:

74140

show subpopulations

African (AFR)

AF:

0.00254

AC:

105

AN:

41384

American (AMR)

AF:

0.00794

AC:

121

AN:

15246

Ashkenazi Jewish (ASJ)

AF:

0.00923

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5160

South Asian (SAS)

AF:

0.00291

AC:

AN:

4808

European-Finnish (FIN)

AF:

0.00220

AC:

AN:

10452

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0116

AC:

790

AN:

67922

Other (OTH)

AF:

0.00760

AC:

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

118

177

236

295

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00981

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

Jan 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

(source)

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

PhyloP100

2.8

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

Mutation Taster

=84/16

polymorphism

(source)

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

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rs118077502

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over