6-121080878-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_152730.6(TBC1D32):c.3667C>T(p.His1223Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00237 in 1,610,332 control chromosomes in the GnomAD database, including 20 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0026 ( 1 hom., cov: 31)

Exomes 𝑓: 0.0023 ( 19 hom. )

Consequence

TBC1D32
NM_152730.6 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 2.11

Publications

7 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 -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009585798).

BP6

Variant 6-121080878-G-A is Benign according to our data. Variant chr6-121080878-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 781887.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAdExome4 at 19 AR,Unknown gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBC1D32	NM_152730.6 link	c.3667C>T	p.His1223Tyr	missense_variant	Exon 32 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.3667C>T	p.His1223Tyr	missense_variant	Exon 32 of 32	5	NM_152730.6	ENSP00000381270.2	Q96NH3-1
TBC1D32	ENST00000275159.11 link	c.3790C>T	p.His1264Tyr	missense_variant	Exon 33 of 33	5		ENSP00000275159.6	Q96NH3-4
TBC1D32	ENST00000464622.5 link	n.*4307C>T		non_coding_transcript_exon_variant	Exon 36 of 36	2		ENSP00000428839.1	Q96NH3-5
TBC1D32	ENST00000464622.5 link	n.*4307C>T		3_prime_UTR_variant	Exon 36 of 36	2		ENSP00000428839.1	Q96NH3-5

Frequencies

GnomAD3 genomes

AF:

0.00258

AC:

392

AN:

152114

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00660

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00448

Gnomad OTH

AF:

0.00191

GnomAD2 exomes

AF:

0.00283

AC:

695

AN:

245748

AF XY:

0.00279

show subpopulations

Gnomad AFR exome

AF:

0.000130

Gnomad AMR exome

AF:

0.000387

Gnomad ASJ exome

AF:

0.00232

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00888

Gnomad NFE exome

AF:

0.00403

Gnomad OTH exome

AF:

0.00251

GnomAD4 exome

AF:

0.00235

AC:

3425

AN:

1458100

Hom.:

Cov.:

AF XY:

0.00241

AC XY:

1747

AN XY:

725166

show subpopulations

African (AFR)

AF:

0.000120

AC:

AN:

33284

American (AMR)

AF:

0.000434

AC:

AN:

43776

Ashkenazi Jewish (ASJ)

AF:

0.00189

AC:

AN:

25994

East Asian (EAS)

AF:

0.00

AC:

AN:

39636

South Asian (SAS)

AF:

0.00

AC:

AN:

85116

European-Finnish (FIN)

AF:

0.00890

AC:

475

AN:

53364

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5752

European-Non Finnish (NFE)

AF:

0.00247

AC:

2743

AN:

1110904

Other (OTH)

AF:

0.00224

AC:

135

AN:

60274

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

160

319

479

638

798

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00258

AC:

392

AN:

152232

Hom.:

Cov.:

AF XY:

0.00259

AC XY:

193

AN XY:

74426

show subpopulations

African (AFR)

AF:

0.000120

AC:

AN:

41536

American (AMR)

AF:

0.000262

AC:

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.00115

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00

AC:

AN:

4814

European-Finnish (FIN)

AF:

0.00660

AC:

AN:

10606

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00448

AC:

305

AN:

68026

Other (OTH)

AF:

0.00189

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

108

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00357

Hom.:

Bravo

AF:

0.00161

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.000269

AC:

ESP6500EA

AF:

0.00219

AC:

ExAC

AF:

0.00274

AC:

331

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00285

EpiControl

AF:

0.00197

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Mar 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

TBC1D32: BP4, BS2 -

Jan 24, 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

0.080

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.48

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.070

.;T

Eigen

Uncertain

0.27

Eigen_PC

Uncertain

0.37

FATHMM_MKL

Uncertain

0.84

LIST_S2

Benign

0.69

T;T

M_CAP

Benign

0.0048

MetaRNN

Benign

0.0096

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.9

.;L

PhyloP100

2.1

PROVEAN

Benign

-2.1

N;N

REVEL

Benign

0.063

Sift

Benign

0.042

D;D

Sift4G

Uncertain

0.017

D;D

Polyphen

0.71

.;P

Vest4

0.21

MVP

0.53

MPC

0.041

ClinPred

0.018

GERP RS

5.5

Varity_R

0.13

gMVP

0.083

Mutation Taster

=99/1

polymorphism

(source)

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

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6-121080878-G-A

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