13-112554080-G-T

Variant names:

• chr13-112554080-G-T
• rs142891996
• NM_006322.6:c.943C>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_006322.6(TUBGCP3):​c.943C>A​(p.Arg315Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R315C) has been classified 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: 6.99
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 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
TUBGCP3	NM_006322.6	c.943C>A	p.Arg315Ser	missense_variant	Exon 8 of 22	ENST00000261965.8	NP_006313.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TUBGCP3	ENST00000261965.8	c.943C>A	p.Arg315Ser	missense_variant	Exon 8 of 22	1	NM_006322.6	ENSP00000261965.3
TUBGCP3	ENST00000375669.7	c.943C>A	p.Arg315Ser	missense_variant	Exon 8 of 21	1		ENSP00000364821.3
TUBGCP3	ENST00000464139.5	c.943C>A	p.Arg315Ser	missense_variant	Exon 8 of 10	1		ENSP00000478276.1
TUBGCP3	ENST00000649778.1	n.943C>A		non_coding_transcript_exon_variant	Exon 8 of 23			ENSP00000497715.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jul 31, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.943C>A (p.R315S) alteration is located in exon 8 (coding exon 8) of the TUBGCP3 gene. This alteration results from a C to A substitution at nucleotide position 943, causing the arginine (R) at amino acid position 315 to be replaced by a serine (S). 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	0.61
BayesDel_addAF	Uncertain	0.012	T
BayesDel_noAF	Benign	-0.22
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.055	T;.;T
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.084
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.97	D;D;D
M_CAP	Benign	0.015	T
MetaRNN	Uncertain	0.70	D;D;D
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.52	N;N;.
PhyloP100		7.0
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-1.7	N;N;.
REVEL	Benign	0.21
Sift	Benign	0.061	T;D;.
Sift4G	Benign	0.30	T;T;D
Polyphen		0.0080	B;B;.
Vest4		0.73
MutPred		0.62		Gain of catalytic residue at G318 (P = 0.0028);Gain of catalytic residue at G318 (P = 0.0028);Gain of catalytic residue at G318 (P = 0.0028);
MVP		0.53
MPC		0.60
ClinPred		0.85	D
GERP RS		4.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.66
gMVP		0.58
Mutation Taster		=55/45	polymorphism

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

Other links and lift over

dbSNP: rs142891996; hg19: chr13-113208394;