Genetic Variant TBCCD1:p.Gly477Gly (chr3-186554367-C-T) – ACMG Classification: Benign (-19 pts)

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_018138.5(TBCCD1):c.1431G>A(p.Gly477Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00394 in 1,614,126 control chromosomes in the GnomAD database, including 197 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.020 ( 100 hom., cov: 32)

Exomes 𝑓: 0.0023 ( 97 hom. )

Consequence

TBCCD1
NM_018138.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.26

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.34).

BP6

Variant 3-186554367-C-T is Benign according to our data. Variant chr3-186554367-C-T is described in ClinVar as [Benign]. Clinvar id is 781974.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.26 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0662 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBCCD1	NM_018138.5 link	c.1431G>A	p.Gly477Gly	synonymous_variant	Exon 6 of 8	ENST00000338733.10	NP_060608.1	Q9NVR7-1
TBCCD1	NM_001134415.1 link	c.1431G>A	p.Gly477Gly	synonymous_variant	Exon 6 of 8		NP_001127887.1	Q9NVR7-1
TBCCD1	NM_001286749.2 link	c.1143G>A	p.Gly381Gly	synonymous_variant	Exon 5 of 7		NP_001273678.1	Q9NVR7-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
TBCCD1	ENST00000338733.10 link	c.1431G>A	p.Gly477Gly	synonymous_variant	Exon 6 of 8	1	NM_018138.5	ENSP00000341652.5	Q9NVR7-1
TBCCD1	ENST00000424280.5 link	c.1431G>A	p.Gly477Gly	synonymous_variant	Exon 6 of 8	5		ENSP00000411253.1	Q9NVR7-1
TBCCD1	ENST00000446782.5 link	c.1143G>A	p.Gly381Gly	synonymous_variant	Exon 5 of 7	2		ENSP00000397091.1	Q9NVR7-2
TBCCD1	ENST00000479590.1 link	n.109G>A		non_coding_transcript_exon_variant	Exon 1 of 2	3

Frequencies

GnomAD3 genomes

AF:

0.0196

AC:

2985

AN:

152116

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0680

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00707

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000323

Gnomad OTH

AF:

0.0125

GnomAD3 exomes

AF:

0.00563

AC:

1415

AN:

251410

Hom.:

AF XY:

0.00408

AC XY:

555

AN XY:

135894

show subpopulations

Gnomad AFR exome

AF:

0.0696

Gnomad AMR exome

AF:

0.00593

Gnomad ASJ exome

AF:

0.00179

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000980

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000281

Gnomad OTH exome

AF:

0.00440

GnomAD4 exome

AF:

0.00229

AC:

3346

AN:

1461892

Hom.:

Cov.:

AF XY:

0.00199

AC XY:

1445

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.0741

Gnomad4 AMR exome

AF:

0.00664

Gnomad4 ASJ exome

AF:

0.00203

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000156

Gnomad4 OTH exome

AF:

0.00503

GnomAD4 genome

AF:

0.0197

AC:

3006

AN:

152234

Hom.:

100

Cov.:

AF XY:

0.0187

AC XY:

1395

AN XY:

74420

show subpopulations

Gnomad4 AFR

AF:

0.0683

Gnomad4 AMR

AF:

0.00706

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000416

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000323

Gnomad4 OTH

AF:

0.0123

Alfa

AF:

0.00999

Hom.:

Bravo

AF:

0.0228

Asia WGS

AF:

0.00260

AC:

AN:

3478

EpiCase

AF:

0.000654

EpiControl

AF:

0.000474

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jul 18, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.34

CADD

Benign

DANN

Benign

0.66

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.15

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