6-121080850-T-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_152730.6(TBC1D32):c.3695A>C(p.Glu1232Ala) variant causes a missense change. The variant allele was found at a frequency of 0.0163 in 1,613,910 control chromosomes in the GnomAD database, including 258 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.014 ( 14 hom., cov: 31)

Exomes 𝑓: 0.017 ( 244 hom. )

Consequence

TBC1D32
NM_152730.6 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 4.16

Publications

13 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0055611134).

BP6

Variant 6-121080850-T-G is Benign according to our data. Variant chr6-121080850-T-G is described in ClinVar as [Benign]. Clinvar id is 1541792.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.0144 (2195/152288) while in subpopulation SAS AF = 0.0191 (92/4828). AF 95% confidence interval is 0.0159. There are 14 homozygotes in GnomAd4. There are 1037 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 14 AR,Unknown gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBC1D32	NM_152730.6 link	c.3695A>C	p.Glu1232Ala	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.3695A>C	p.Glu1232Ala	missense_variant	Exon 32 of 32	5	NM_152730.6	ENSP00000381270.2	Q96NH3-1
TBC1D32	ENST00000275159.11 link	c.3818A>C	p.Glu1273Ala	missense_variant	Exon 33 of 33	5		ENSP00000275159.6	Q96NH3-4
TBC1D32	ENST00000464622.5 link	n.*4335A>C		non_coding_transcript_exon_variant	Exon 36 of 36	2		ENSP00000428839.1	Q96NH3-5
TBC1D32	ENST00000464622.5 link	n.*4335A>C		3_prime_UTR_variant	Exon 36 of 36	2		ENSP00000428839.1	Q96NH3-5

Frequencies

GnomAD3 genomes

AF:

0.0144

AC:

2196

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0141

Gnomad AMI

AF:

0.00658

Gnomad AMR

AF:

0.0120

Gnomad ASJ

AF:

0.00806

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.0197

Gnomad FIN

AF:

0.0106

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.0167

Gnomad OTH

AF:

0.0172

GnomAD2 exomes

AF:

0.0146

AC:

3634

AN:

248718

AF XY:

0.0155

show subpopulations

Gnomad AFR exome

AF:

0.0135

Gnomad AMR exome

AF:

0.00949

Gnomad ASJ exome

AF:

0.00757

Gnomad EAS exome

AF:

0.0000558

Gnomad FIN exome

AF:

0.0139

Gnomad NFE exome

AF:

0.0172

Gnomad OTH exome

AF:

0.0153

GnomAD4 exome

AF:

0.0165

AC:

24149

AN:

1461622

Hom.:

244

Cov.:

AF XY:

0.0169

AC XY:

12265

AN XY:

727104

show subpopulations

African (AFR)

AF:

0.0156

AC:

523

AN:

33468

American (AMR)

AF:

0.0105

AC:

469

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.00773

AC:

202

AN:

26124

East Asian (EAS)

AF:

0.00

AC:

AN:

39674

South Asian (SAS)

AF:

0.0223

AC:

1920

AN:

86230

European-Finnish (FIN)

AF:

0.0136

AC:

727

AN:

53394

Middle Eastern (MID)

AF:

0.0281

AC:

162

AN:

5766

European-Non Finnish (NFE)

AF:

0.0173

AC:

19209

AN:

1111864

Other (OTH)

AF:

0.0155

AC:

937

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

1203

2405

3608

4810

6013

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0144

AC:

2195

AN:

152288

Hom.:

Cov.:

AF XY:

0.0139

AC XY:

1037

AN XY:

74462

show subpopulations

African (AFR)

AF:

0.0142

AC:

590

AN:

41568

American (AMR)

AF:

0.0119

AC:

182

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.00806

AC:

AN:

3472

East Asian (EAS)

AF:

0.000387

AC:

AN:

5174

South Asian (SAS)

AF:

0.0191

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.0106

AC:

113

AN:

10622

Middle Eastern (MID)

AF:

0.0306

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0167

AC:

1137

AN:

68022

Other (OTH)

AF:

0.0170

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

113

226

338

451

564

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0164

Hom.:

Bravo

AF:

0.0140

TwinsUK

AF:

0.0170

AC:

ALSPAC

AF:

0.0161

AC:

ESP6500AA

AF:

0.0117

AC:

ESP6500EA

AF:

0.0156

AC:

129

ExAC

AF:

0.0146

AC:

1760

Asia WGS

AF:

0.0110

AC:

AN:

3478

EpiCase

AF:

0.0201

EpiControl

AF:

0.0168

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jan 08, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

May 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

TBC1D32: BP4, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.35

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.058

.;T

Eigen

Benign

0.10

Eigen_PC

Uncertain

0.26

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.86

D;D

MetaRNN

Benign

0.0056

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.6

.;M

PhyloP100

4.2

PROVEAN

Benign

-2.1

N;N

REVEL

Benign

0.047

Sift

Uncertain

0.0090

D;D

Sift4G

Uncertain

0.030

D;D

Polyphen

0.095

.;B

Vest4

0.19

MPC

0.17

ClinPred

0.041

GERP RS

5.5

Varity_R

0.19

gMVP

0.18

Mutation Taster

=89/11

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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6-121080850-T-G

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