Variant 3-186554506-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_018138.5(TBCCD1):c.1292C>T(p.Ala431Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000204 in 1,614,120 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000021 ( 0 hom. )

Consequence

TBCCD1
NM_018138.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.46

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 Likely_pathogenic. Variant got 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.95

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TBCCD1	NM_018138.5 link	c.1292C>T	p.Ala431Val	missense_variant	6/8	ENST00000338733.10	NP_060608.1	Q9NVR7-1
TBCCD1	NM_001134415.1 link	c.1292C>T	p.Ala431Val	missense_variant	6/8		NP_001127887.1	Q9NVR7-1
TBCCD1	NM_001286749.2 link	c.1004C>T	p.Ala335Val	missense_variant	5/7		NP_001273678.1	Q9NVR7-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TBCCD1	ENST00000338733.10 link	c.1292C>T	p.Ala431Val	missense_variant	6/8	1	NM_018138.5	ENSP00000341652.5	Q9NVR7-1
TBCCD1	ENST00000424280.5 link	c.1292C>T	p.Ala431Val	missense_variant	6/8	5		ENSP00000411253.1	Q9NVR7-1
TBCCD1	ENST00000446782.5 link	c.1004C>T	p.Ala335Val	missense_variant	5/7	2		ENSP00000397091.1	Q9NVR7-2
TBCCD1	ENST00000479590.1 link	n.-31C>T		upstream_gene_variant		3

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152238

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000205

AC:

AN:

1461882

Hom.:

Cov.:

AF XY:

0.0000206

AC XY:

AN XY:

727240

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

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:

0.0000252

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152238

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74376

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000189

ExAC

AF:

0.00000824

AC:

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

Jan 10, 2022

The c.1292C>T (p.A431V) alteration is located in exon 6 (coding exon 5) of the TBCCD1 gene. This alteration results from a C to T substitution at nucleotide position 1292, causing the alanine (A) at amino acid position 431 to be replaced by a valine (V). 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

Uncertain

0.52

BayesDel_addAF

Uncertain

0.16

BayesDel_noAF

Uncertain

-0.010

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.60

D;D;.

Eigen

Uncertain

0.56

Eigen_PC

Uncertain

0.59

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.96

D;.;D

M_CAP

Benign

0.058

MetaRNN

Pathogenic

0.95

D;D;D

MetaSVM

Uncertain

0.30

MutationAssessor

Uncertain

2.4

M;M;.

PrimateAI

Uncertain

0.63

PROVEAN

Uncertain

-2.5

N;N;N

REVEL

Uncertain

0.63

Sift

Uncertain

0.018

D;D;D

Sift4G

Uncertain

0.010

D;D;D

Polyphen

0.92

P;P;.

Vest4

0.63

MutPred

0.87

Gain of glycosylation at T433 (P = 0.0826);Gain of glycosylation at T433 (P = 0.0826);.;

MVP

0.83

MPC

0.59

ClinPred

0.97

GERP RS

4.9

Varity_R

0.32

gMVP

0.58

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