3-186551192-G-C

Position:

• chr3-186551192-G-C

Variant summary

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

The ENST00000338733.10(TBCCD1):​c.1632C>G​(p.Ser544Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TBCCD1 ENST00000338733.10 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.00

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]

ACMG classification

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/exons	MANE	Protein	UniProt
TBCCD1	NM_018138.5	c.1632C>G	p.Ser544Arg	missense_variant	7/8	ENST00000338733.10	NP_060608.1
TBCCD1	NM_001134415.1	c.1632C>G	p.Ser544Arg	missense_variant	7/8		NP_001127887.1
TBCCD1	NM_001286749.2	c.1344C>G	p.Ser448Arg	missense_variant	6/7		NP_001273678.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TBCCD1	ENST00000338733.10	c.1632C>G	p.Ser544Arg	missense_variant	7/8	1	NM_018138.5	ENSP00000341652.5
TBCCD1	ENST00000424280.5	c.1632C>G	p.Ser544Arg	missense_variant	7/8	5		ENSP00000411253.1
TBCCD1	ENST00000446782.5	c.1344C>G	p.Ser448Arg	missense_variant	6/7	2		ENSP00000397091.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 29, 2022

The c.1632C>G (p.S544R) alteration is located in exon 7 (coding exon 6) of the TBCCD1 gene. This alteration results from a C to G substitution at nucleotide position 1632, causing the serine (S) at amino acid position 544 to be replaced by an arginine (R). 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	Pathogenic	0.85
BayesDel_addAF	Pathogenic	0.35	D
BayesDel_noAF	Pathogenic	0.26
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.17	T;T;.
Eigen	Uncertain	0.35
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.90	D;.;D
M_CAP	Uncertain	0.094	D
MetaRNN	Uncertain	0.66	D;D;D
MetaSVM	Uncertain	0.21	D
MutationAssessor	Uncertain	2.5	M;M;.
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-1.7	N;N;N
REVEL	Uncertain	0.55
Sift	Benign	0.087	T;T;T
Sift4G	Benign	0.063	T;T;T
Polyphen		1.0	D;D;.
Vest4		0.89
MutPred		0.23		Loss of glycosylation at S544 (P = 0.0309);Loss of glycosylation at S544 (P = 0.0309);.;
MVP		0.81
MPC		0.65
ClinPred		0.95	D
GERP RS		1.1
Varity_R		0.23
gMVP		0.54

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

Other links and lift over

dbSNP: rs1714363580; hg19: chr3-186268981;