13-112519016-C-A

Position:

• chr13-112519016-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_006322.6(TUBGCP3):​c.1909G>T​(p.Val637Phe) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: TUBGCP3 NM_006322.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.02

Genes affected

TUBGCP3 (HGNC:18598): (tubulin gamma complex component 3) Enables gamma-tubulin binding activity. Predicted to be involved in meiotic cell cycle; microtubule cytoskeleton organization; and mitotic cell cycle. Located in cytoplasm and microtubule cytoskeleton. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.854

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TUBGCP3	NM_006322.6	c.1909G>T	p.Val637Phe	missense_variant	16/22	ENST00000261965.8	NP_006313.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TUBGCP3	ENST00000261965.8	c.1909G>T	p.Val637Phe	missense_variant	16/22	1	NM_006322.6	ENSP00000261965	P1
TUBGCP3	ENST00000375669.7	c.1909G>T	p.Val637Phe	missense_variant	16/21	1		ENSP00000364821
TUBGCP3	ENST00000649778.1	c.*272G>T		3_prime_UTR_variant, NMD_transcript_variant	17/23			ENSP00000497715

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 33

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 25, 2024

The c.1909G>T (p.V637F) alteration is located in exon 16 (coding exon 16) of the TUBGCP3 gene. This alteration results from a G to T substitution at nucleotide position 1909, causing the valine (V) at amino acid position 637 to be replaced by a phenylalanine (F). 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	1.0
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.090
CADD	Pathogenic	29
DANN	Uncertain	0.99
DEOGEN2	Benign	0.25	T;.
Eigen	Pathogenic	0.72
Eigen_PC	Uncertain	0.65
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.97	D;D
M_CAP	Benign	0.030	D
MetaRNN	Pathogenic	0.85	D;D
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.8	M;M
MutationTaster	Benign	1.0	D;D
PrimateAI	Pathogenic	0.83	D
PROVEAN	Uncertain	-4.1	D;D
REVEL	Uncertain	0.50
Sift	Uncertain	0.0020	D;D
Sift4G	Uncertain	0.0020	D;D
Polyphen		1.0	D;P
Vest4		0.91
MutPred		0.59		Gain of catalytic residue at D641 (P = 6e-04);Gain of catalytic residue at D641 (P = 6e-04);
MVP		0.69
MPC		1.6
ClinPred		0.99	D
GERP RS		5.4
Varity_R		0.87
gMVP		0.90

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: chr13-113173330;