Variant 3-186556751-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000338733.10(TBCCD1):c.517G>A(p.Ala173Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000821 in 1,461,684 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000082 ( 0 hom. )

Consequence

TBCCD1
ENST00000338733.10 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.92

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.026952535).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TBCCD1	NM_018138.5 linkuse as main transcript	c.517G>A	p.Ala173Thr	missense_variant	4/8	ENST00000338733.10	NP_060608.1	Q9NVR7-1
TBCCD1	NM_001134415.1 linkuse as main transcript	c.517G>A	p.Ala173Thr	missense_variant	4/8		NP_001127887.1	Q9NVR7-1
TBCCD1	NM_001286749.2 linkuse as main transcript	c.229G>A	p.Ala77Thr	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.517G>A	p.Ala173Thr	missense_variant	4/8	1	NM_018138.5	ENSP00000341652.5	Q9NVR7-1
TBCCD1	ENST00000424280.5 linkuse as main transcript	c.517G>A	p.Ala173Thr	missense_variant	4/8	5		ENSP00000411253.1	Q9NVR7-1
TBCCD1	ENST00000446782.5 linkuse as main transcript	c.229G>A	p.Ala77Thr	missense_variant	3/7	2		ENSP00000397091.1	Q9NVR7-2
TBCCD1	ENST00000413695.1 linkuse as main transcript	c.517G>A	p.Ala173Thr	missense_variant	4/4	3		ENSP00000391109.1	C9J4M0

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000398

AC:

AN:

251146

Hom.:

AF XY:

0.0000442

AC XY:

AN XY:

135736

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000544

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:

0.00000821

AC:

AN:

1461684

Hom.:

Cov.:

AF XY:

0.0000110

AC XY:

AN XY:

727126

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000277

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000264

ExAC

AF:

0.0000494

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

Oct 03, 2023

The c.517G>A (p.A173T) 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 517, causing the alanine (A) at amino acid position 173 to be replaced by a threonine (T). 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

Benign

0.074

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.47

CADD

Benign

DANN

Benign

0.72

DEOGEN2

Benign

0.061

T;T;.;T

Eigen

Benign

-0.59

Eigen_PC

Benign

-0.42

FATHMM_MKL

Benign

0.61

LIST_S2

Benign

0.69

T;.;T;T

M_CAP

Benign

0.0083

MetaRNN

Benign

0.027

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.91

L;L;.;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.36

PROVEAN

Benign

-0.16

N;N;N;N

REVEL

Benign

0.072

Sift

Benign

0.66

T;T;T;T

Sift4G

Benign

0.40

T;T;T;T

Polyphen

0.0

B;B;.;.

Vest4

0.12

MutPred

0.15

Gain of loop (P = 0.1069);Gain of loop (P = 0.1069);.;Gain of loop (P = 0.1069);

MVP

0.35

MPC

0.14

ClinPred

0.024

GERP RS

2.8

Varity_R

0.038

gMVP

0.21

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