chr3-186556643-C-G

Position:

• chr3-186556643-C-G

Variant summary

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

The ENST00000338733.10(TBCCD1):​c.625G>C​(p.Val209Leu) 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: 3.31

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.625G>C	p.Val209Leu	missense_variant	4/8	ENST00000338733.10	NP_060608.1
TBCCD1	NM_001134415.1	c.625G>C	p.Val209Leu	missense_variant	4/8		NP_001127887.1
TBCCD1	NM_001286749.2	c.337G>C	p.Val113Leu	missense_variant	3/7		NP_001273678.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TBCCD1	ENST00000338733.10	c.625G>C	p.Val209Leu	missense_variant	4/8	1	NM_018138.5	ENSP00000341652.5
TBCCD1	ENST00000424280.5	c.625G>C	p.Val209Leu	missense_variant	4/8	5		ENSP00000411253.1
TBCCD1	ENST00000446782.5	c.337G>C	p.Val113Leu	missense_variant	3/7	2		ENSP00000397091.1
TBCCD1	ENST00000413695.1	c.625G>C	p.Val209Leu	missense_variant	4/4	3		ENSP00000391109.1

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

Mar 23, 2023

The c.625G>C (p.V209L) alteration is located in exon 4 (coding exon 3) of the TBCCD1 gene. This alteration results from a G to C substitution at nucleotide position 625, causing the valine (V) at amino acid position 209 to be replaced by a leucine (L). 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	0.23
BayesDel_addAF	Uncertain	0.099	D
BayesDel_noAF	Benign	-0.10
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.14	T;T;.;T
Eigen	Uncertain	0.59
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.85	T;.;T;T
M_CAP	Benign	0.071	D
MetaRNN	Uncertain	0.71	D;D;D;D
MetaSVM	Uncertain	-0.094	T
MutationAssessor	Uncertain	2.6	M;M;.;.
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-1.6	N;N;N;N
REVEL	Uncertain	0.53
Sift	Uncertain	0.0070	D;D;D;D
Sift4G	Pathogenic	0.0	D;D;D;D
Polyphen		1.0	D;D;.;.
Vest4		0.29
MutPred		0.68		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		0.68
MPC		0.22
ClinPred		0.82	D
GERP RS		4.7
Varity_R		0.33
gMVP		0.60

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-186274432;