Variant 3-186556645-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_018138.5(TBCCD1):c.623C>T(p.Ala208Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000124 in 1,614,048 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

TBCCD1
NM_018138.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.85

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.26254982).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
TBCCD1	NM_018138.5 linkuse as main transcript	c.623C>T	p.Ala208Val	missense_variant	4/8	ENST00000338733.10	NP_060608.1
TBCCD1	NM_001134415.1 linkuse as main transcript	c.623C>T	p.Ala208Val	missense_variant	4/8		NP_001127887.1
TBCCD1	NM_001286749.2 linkuse as main transcript	c.335C>T	p.Ala112Val	missense_variant	3/7		NP_001273678.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TBCCD1	ENST00000338733.10 linkuse as main transcript	c.623C>T	p.Ala208Val	missense_variant	4/8	1	NM_018138.5	ENSP00000341652	P1	Q9NVR7-1
TBCCD1	ENST00000424280.5 linkuse as main transcript	c.623C>T	p.Ala208Val	missense_variant	4/8	5		ENSP00000411253	P1	Q9NVR7-1
TBCCD1	ENST00000446782.5 linkuse as main transcript	c.335C>T	p.Ala112Val	missense_variant	3/7	2		ENSP00000397091		Q9NVR7-2
TBCCD1	ENST00000413695.1 linkuse as main transcript	c.623C>T	p.Ala208Val	missense_variant	4/4	3		ENSP00000391109

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461880

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.00

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:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152168

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74330

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

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

Apr 12, 2023

The c.623C>T (p.A208V) alteration is located in exon 4 (coding exon 3) of the TBCCD1 gene. This alteration results from a C to T substitution at nucleotide position 623, causing the alanine (A) at amino acid position 208 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

Benign

0.20

BayesDel_addAF

Uncertain

0.038

BayesDel_noAF

Benign

-0.18

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.17

T;T;.;T

Eigen

Benign

-0.10

Eigen_PC

Benign

0.088

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.87

D;.;D;D

M_CAP

Benign

0.016

MetaRNN

Benign

0.26

T;T;T;T

MetaSVM

Benign

-0.88

MutationAssessor

Benign

1.4

L;L;.;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-2.2

N;N;N;N

REVEL

Benign

0.28

Sift

Benign

0.21

T;T;T;T

Sift4G

Benign

0.34

T;T;T;T

Polyphen

0.014

B;B;.;.

Vest4

0.49

MutPred

0.32

Gain of glycosylation at S205 (P = 0.0941);Gain of glycosylation at S205 (P = 0.0941);.;Gain of glycosylation at S205 (P = 0.0941);

MVP

0.64

MPC

0.15

ClinPred

0.75

GERP RS

4.7

Varity_R

0.059

gMVP

0.62

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