Variant 13-112516502-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PP3_ModerateBS2

The NM_006322.6(TUBGCP3):c.2024A>G(p.Tyr675Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000301 in 1,461,670 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)

Exomes 𝑓: 0.000030 ( 0 hom. )

Consequence

TUBGCP3
NM_006322.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.31

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 Likely_benign. Variant got -2 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.858

BS2

High AC in GnomAdExome4 at 44 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TUBGCP3	NM_006322.6 linkuse as main transcript	c.2024A>G	p.Tyr675Cys	missense_variant	17/22	ENST00000261965.8	NP_006313.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TUBGCP3	ENST00000261965.8 linkuse as main transcript	c.2024A>G	p.Tyr675Cys	missense_variant	17/22	1	NM_006322.6	ENSP00000261965	P1	Q96CW5-1
TUBGCP3	ENST00000375669.7 linkuse as main transcript	c.2024A>G	p.Tyr675Cys	missense_variant	17/21	1		ENSP00000364821		Q96CW5-2
TUBGCP3	ENST00000649778.1 linkuse as main transcript	c.*387A>G		3_prime_UTR_variant, NMD_transcript_variant	18/23			ENSP00000497715

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.0000301

AC:

AN:

1461670

Hom.:

Cov.:

AF XY:

0.0000193

AC XY:

AN XY:

727092

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000369

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000312

Hom.:

Bravo

AF:

0.00000378

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00000824

AC:

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

Aug 01, 2022

The c.2024A>G (p.Y675C) 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 2024, causing the tyrosine (Y) at amino acid position 675 to be replaced by a cysteine (C). 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

Uncertain

0.52

BayesDel_addAF

Pathogenic

0.22

BayesDel_noAF

Uncertain

0.070

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.21

T;.

Eigen

Uncertain

0.59

Eigen_PC

Uncertain

0.56

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Pathogenic

0.98

D;D

M_CAP

Benign

0.028

MetaRNN

Pathogenic

0.86

D;D

MetaSVM

Benign

-1.1

MutationAssessor

Benign

2.0

M;M

MutationTaster

Benign

1.0

D;D

PrimateAI

Pathogenic

0.92

PROVEAN

Pathogenic

-5.7

D;D

REVEL

Uncertain

0.53

Sift

Uncertain

0.0030

D;D

Sift4G

Uncertain

0.0080

D;D

Polyphen

0.94

P;P

Vest4

0.90

MVP

0.69

MPC

1.5

ClinPred

0.99

GERP RS

5.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.64

gMVP

0.75

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