Variant 13-112516488-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000261965.8(TUBGCP3):c.2038A>G(p.Ile680Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000131 in 152,224 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)

Consequence

TUBGCP3
ENST00000261965.8 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.62

Variant links:

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]

TUBGCP3 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.24671412).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TUBGCP3	NM_006322.6 linkuse as main transcript	c.2038A>G	p.Ile680Val	missense_variant	17/22	ENST00000261965.8	NP_006313.1	Q96CW5-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TUBGCP3	ENST00000261965.8 linkuse as main transcript	c.2038A>G	p.Ile680Val	missense_variant	17/22	1	NM_006322.6	ENSP00000261965.3	Q96CW5-1
TUBGCP3	ENST00000375669.7 linkuse as main transcript	c.2038A>G	p.Ile680Val	missense_variant	17/21	1		ENSP00000364821.3	Q96CW5-2
TUBGCP3	ENST00000649778.1 linkuse as main transcript	n.*401A>G		non_coding_transcript_exon_variant	18/23			ENSP00000497715.1	A0A3B3ITE3
TUBGCP3	ENST00000649778.1 linkuse as main transcript	n.*401A>G		3_prime_UTR_variant	18/23			ENSP00000497715.1	A0A3B3ITE3

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152224

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152224

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74362

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 13, 2023

The c.2038A>G (p.I680V) alteration is located in exon 17 (coding exon 17) of the TUBGCP3 gene. This alteration results from a A to G substitution at nucleotide position 2038, causing the isoleucine (I) at amino acid position 680 to be replaced by a valine (V). 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

0.11

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.050

T;.

Eigen

Benign

-0.18

Eigen_PC

Benign

-0.083

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.82

T;T

M_CAP

Benign

0.0090

MetaRNN

Benign

0.25

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

L;L

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.65

PROVEAN

Benign

-0.26

N;N

REVEL

Benign

0.10

Sift

Benign

0.11

T;T

Sift4G

Benign

0.18

T;T

Polyphen

0.59

P;B

Vest4

0.25

MutPred

0.67

Gain of catalytic residue at K682 (P = 0.0037);Gain of catalytic residue at K682 (P = 0.0037);

MVP

0.21

MPC

0.47

ClinPred

0.38

GERP RS

4.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.7

Varity_R

0.092

gMVP

0.21

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

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