Variant chr3-186556540-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000338733.10(TBCCD1):c.728G>A(p.Gly243Asp) variant causes a missense change. The variant allele was found at a frequency of 0.0000143 in 1,613,500 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00012 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

TBCCD1
ENST00000338733.10 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.92

Variant links:

Genes affected

TBCCD1 (HGNC:25546): (TBCC domain containing 1) Involved in several processes, including maintenance of Golgi location; maintenance of centrosome location; and regulation of cell shape. Located in spindle pole centrosome. [provided by Alliance of Genome Resources, Apr 2022]

TBCCD1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TBCCD1	NM_018138.5 linkuse as main transcript	c.728G>A	p.Gly243Asp	missense_variant	4/8	ENST00000338733.10	NP_060608.1	Q9NVR7-1
TBCCD1	NM_001134415.1 linkuse as main transcript	c.728G>A	p.Gly243Asp	missense_variant	4/8		NP_001127887.1	Q9NVR7-1
TBCCD1	NM_001286749.2 linkuse as main transcript	c.440G>A	p.Gly147Asp	missense_variant	3/7		NP_001273678.1	Q9NVR7-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TBCCD1	ENST00000338733.10 linkuse as main transcript	c.728G>A	p.Gly243Asp	missense_variant	4/8	1	NM_018138.5	ENSP00000341652.5	Q9NVR7-1
TBCCD1	ENST00000424280.5 linkuse as main transcript	c.728G>A	p.Gly243Asp	missense_variant	4/8	5		ENSP00000411253.1	Q9NVR7-1
TBCCD1	ENST00000446782.5 linkuse as main transcript	c.440G>A	p.Gly147Asp	missense_variant	3/7	2		ENSP00000397091.1	Q9NVR7-2
TBCCD1	ENST00000413695.1 linkuse as main transcript	c.*50G>A		downstream_gene_variant		3		ENSP00000391109.1	C9J4M0

Frequencies

GnomAD3 genomes

AF:

0.000118

AC:

AN:

152158

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00118

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000120

AC:

AN:

250876

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

135588

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000872

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000342

AC:

AN:

1461342

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726964

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000897

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.000118

AC:

AN:

152158

Hom.:

Cov.:

AF XY:

0.000229

AC XY:

AN XY:

74338

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00118

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.000106

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 27, 2023

The c.728G>A (p.G243D) alteration is located in exon 4 (coding exon 3) of the TBCCD1 gene. This alteration results from a G to A substitution at nucleotide position 728, causing the glycine (G) at amino acid position 243 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.77

BayesDel_addAF

Pathogenic

0.19

BayesDel_noAF

Pathogenic

0.24

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.14

T;T;.

Eigen

Pathogenic

0.86

Eigen_PC

Pathogenic

0.85

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.83

T;.;T

M_CAP

Benign

0.079

MetaRNN

Uncertain

0.70

D;D;D

MetaSVM

Uncertain

-0.027

MutationAssessor

Uncertain

2.6

M;M;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.65

PROVEAN

Uncertain

-2.5

D;D;D

REVEL

Uncertain

0.44

Sift

Pathogenic

0.0

D;D;D

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

1.0

D;D;.

Vest4

0.93

MutPred

0.36

Gain of ubiquitination at K246 (P = 0.0482);Gain of ubiquitination at K246 (P = 0.0482);.;

MVP

0.80

MPC

0.73

ClinPred

0.96

GERP RS

5.7

Varity_R

0.78

gMVP

0.77

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