3-186555051-C-T

Variant summary

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

The NM_018138.5(TBCCD1):​c.893G>A​(p.Cys298Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,458,266 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

TBCCD1
NM_018138.5 missense

Scores

2
11
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.57
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]

Genome browser will be placed here

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 rank MANE Protein UniProt
TBCCD1NM_018138.5 linkc.893G>A p.Cys298Tyr missense_variant Exon 5 of 8 ENST00000338733.10 NP_060608.1 Q9NVR7-1
TBCCD1NM_001134415.1 linkc.893G>A p.Cys298Tyr missense_variant Exon 5 of 8 NP_001127887.1 Q9NVR7-1
TBCCD1NM_001286749.2 linkc.605G>A p.Cys202Tyr missense_variant Exon 4 of 7 NP_001273678.1 Q9NVR7-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TBCCD1ENST00000338733.10 linkc.893G>A p.Cys298Tyr missense_variant Exon 5 of 8 1 NM_018138.5 ENSP00000341652.5 Q9NVR7-1
TBCCD1ENST00000424280.5 linkc.893G>A p.Cys298Tyr missense_variant Exon 5 of 8 5 ENSP00000411253.1 Q9NVR7-1
TBCCD1ENST00000446782.5 linkc.605G>A p.Cys202Tyr missense_variant Exon 4 of 7 2 ENSP00000397091.1 Q9NVR7-2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000807
AC:
2
AN:
247724
Hom.:
0
AF XY:
0.00000747
AC XY:
1
AN XY:
133874
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000673
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000274
AC:
4
AN:
1458266
Hom.:
0
Cov.:
32
AF XY:
0.00000414
AC XY:
3
AN XY:
725294
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:
0.0000468
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
ExAC
AF:
0.00000824
AC:
1

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Nov 09, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.893G>A (p.C298Y) alteration is located in exon 5 (coding exon 4) of the TBCCD1 gene. This alteration results from a G to A substitution at nucleotide position 893, causing the cysteine (C) at amino acid position 298 to be replaced by a tyrosine (Y). 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
0.41
BayesDel_addAF
Benign
-0.020
T
BayesDel_noAF
Uncertain
-0.080
CADD
Uncertain
26
DANN
Uncertain
1.0
DEOGEN2
Benign
0.17
T;T;.
Eigen
Uncertain
0.68
Eigen_PC
Pathogenic
0.73
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.93
D;.;D
M_CAP
Benign
0.060
D
MetaRNN
Uncertain
0.72
D;D;D
MetaSVM
Uncertain
0.12
D
MutationAssessor
Uncertain
2.3
M;M;.
PrimateAI
Uncertain
0.66
T
PROVEAN
Benign
-2.1
N;N;N
REVEL
Uncertain
0.46
Sift
Benign
0.046
D;D;D
Sift4G
Uncertain
0.054
T;T;D
Polyphen
0.98
D;D;.
Vest4
0.69
MutPred
0.44
Loss of catalytic residue at T300 (P = 0.0658);Loss of catalytic residue at T300 (P = 0.0658);.;
MVP
0.82
MPC
0.69
ClinPred
0.90
D
GERP RS
5.9
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.37
gMVP
0.65

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.11
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.

Other links and lift over

dbSNP: rs775319222; hg19: chr3-186272840; API